Human Genetics Journal Club
Wednesdays 4pm - 4:30pm, Lane L201 (broadcast to Hillview)
Speakers provide a thirty minute presentation with focus on the key findings and important methods from a recent, high-impact article in area of Human and/or Medical Genetics.
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Date: June 21 - Hugh Rienhoff, MD
My Daughter’s DNA….Revealed
June 14 - Melanie Manning, MD
Down Syndrome – There’s Still More To Learn
Reference(s): Am J Med Genet part A 155:1246-1257, "Balanced information about Down syndrome: what is essential?"
Am J Med Genet part A 155:1258-12763, "Understanding physicians' attitudes toward people with Down syndrome"
June 7 - Athena Cherry, PhD
Insertional Translocations: Rare or Common?
Reference(s): Kang et al., "Insertional translocation detected using FISH confirmation of array-comparative genomic hybridization (aCGH) results", American Journal of Medical Genetics, Part A, (2010), 152A:1111-1126
Neill et al., "Recurrence, submicroscopic complexity, and potential clinical relevance of copy gains detected by array CGH that are shown to be unbalanced insertions by FISH", Genome Research (2011), 21:535-544
May 31 - Kelly E. Ormond, MS, LCGC
What’s eMERGE-ing about genomic research ethics? Patient preferences about recontact and reconsent from the eMERGE study
Reference(s): Glad you asked: participants' opinions of re-consent for dbGap data submission. Ludman EJ, et al. J Empir Res Hum Res Ethics. 2010 Sep;5(3):9-16.
Research Practice and Participant Preferences: The Growing Gulf. Trinidad SB et al. Science 21 January 2011: 287-288.
Response—The Risks and Benefits of Re-Consent. Trinidad SB et al. Science 15 April 2011: 306.
May 24 - Jonathan Bernstein, MD, PhD
Mutations in HEPACAM underlie cases of benign familial macrocephaly, macrocephaly-autism syndrome and megencephalic leukoencephalopathy with subcortical cysts.
Reference(s): Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism. López-Hernández T, Ridder MC, Montolio M, Capdevila-Nortes X, Polder E, Sirisi S, Duarri A, Schulte U, Fakler B, Nunes V, Scheper GC, Martínez A, Estévez R, van der Knaap MS. Am J Hum Genet. 2011 Apr 8;88(4):422-32. Epub 2011 Mar 17. PMID: 21419380
May 17 - Lee Kozar
Results from The 1000 Genome Project (and other ways to map human genome variation)
Resource(s): A map of human genome variation from population-scale sequencing. 1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA. Nature, 457:1061-1073 (2010)
May 10 - Andrea Kwan, MS, LCGC
The role of FOXP1 in intellectual disability and speech and language impairment
Reference(s): Hamdan et al, De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010 Nov 12;87(5):671-8. Epub 2010 Oct 14.
Horn D, et al, Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum Mutat. 2010 Nov;31(11):E1851-60.
May 3 - Hui Wang, PhD
Cloud computing: is it the data solution for the next generation sequencing?
Reference(s): Monya Baker. Next-generation sequencing: adjusting to data overload. Nature Methods 7, 495 - 499 (2010)
Lincoln Stein. The case for cloud computing in genome informatics. Genome Biology 2010, 11:207
April 26 - Darrell Wilson, MD (Pediatric Endocrinology)
Heritability of Growth and Pubertal Development
April 19 - Brandon Steelman, MS
The genome ain't flat: unravelling genetic regulation and disease in 3D
Reference(s): Lieberman-Aiden et al. Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome. Science (2009) vol. 326 (5950) pp. 289-293
Schoenfelder et al. Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nature Genetics (2010) vol. 42 (1) pp. 53-61
April 12 - Uta Francke, MD
Growth hormone receptor defect: effects on aging, cancer and diabetes in Ecuador
Reference(s): Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans. Guevara-Aguirre J et al. Science Transl Med 16 February 2011: Vol. 3, Issue 70, p. 70ra13 DOI: 10.1126/scitranslmed.3001845
Date: April 5 - Nilesh Dharajiya, MD
Noninvasive Prenatal Diagnosis by deep sequencing of maternal plasma DNA
Reference(s): Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus. Y. M. Dennis Lo, et al. Sci Transl Med 2, 61ra91 (2010); DOI: 10.1126/scitranslmed.3001720
March 29 - Amrita Ray, MS, PhD
Genetic heterogeneity and pathway in Schizophrenia
Reference(s): Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J. Science. 2008 Apr 25;320(5875):539-43. - PubMed PMID: 18369103
Microduplications of 16p11.2 are associated with schizophrenia. McCarthy SE, et al. Nat Genet. 2009 Nov;41(11):1223-7. - PubMed PMID: 19855392
March 22 - Anna-Kaisa Niemi, MD, PhD
Assembling the etiology of complex III deficiency
Reference(s): "A novel cause gene TTC19 causes mitochondrial complex III deficiency and neurological impairment in humans and flies." Daniele Ghezzi, Paola Arzuffi, Mauro Zordan, Caterina Da Re, Costanza Lamperti, Clara Benna, Pio D'Adamo, Daria Diodato, Rodolfo Costa, Caterina Mariotti, Graziella Uziel, Cristina Smiderle & Massimo Zeviani. Nature Genetics. 2011 Mar;43(3):259-63. Epub 2011 Jan 30.
March 15 - Hua Tang, PhD
Making sense of GWAS hits
Reference(s): MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T, McKenzie LM, Kajiyama H, Ahuja TS, Berns JS, Briggs W, Cho ME, Dart RA, Kimmel PL, Korbet SM, Michel DM, Mokrzycki MH, Schelling JR, Simon E, Trachtman H, Vlahov D, Winkler CA. Nat Genet. 2008 Oct;40(10):1175-84. - PubMed PMID: 18794856
Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR.Science. 2010 Aug 13;329(5993):841-5. Epub 2010 Jul 15. PMID:20647424
March 8 - Kim VandeWydeven
The Discovery of KILLIN and its Role in Cowden and Cowden-like Syndromes
March 1 - Joachim Hallmayer, MD
Forget the parents – it’s de novo
Reference(s): Direct measure of the de novo mutation rate in autism and schizophrenia cohorts. Awadalla P, Gauthier J, Myers RA, Casals F, Hamdan FF, Griffing AR, Côté M, Henrion E, Spiegelman D, Tarabeux J, Piton A, Yang Y, Boyko A, Bustamante C, Xiong L, Rapoport JL, Addington AM, DeLisi JL, Krebs MO, Joober R, Millet B, Fombonne E, Mottron L, Zilversmit M, Keebler J, Daoud H, Marineau C, Roy-Gagnon MH, Dubé MP, Eyre-Walker A, Drapeau P, Stone EA, Lafrenière RG, Rouleau GA. Am J Hum Genet. 2010 Sep 10;87(3):316-24.
A de novo paradigm for mental retardation.
Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, van Lier B, Arts P, Wieskamp N, del Rosario M, van Bon BW, Hoischen A, de Vries BB, Brunner HG, Veltman JA. Nat Genet. 2010 Dec;42(12):1109-1
February 22 - Reana Tischler
Expanded carrier testing using next-generation sequencing
Reference(s): Carrier testing for severe childhood recessive diseases by next-generation sequencing. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, Langley RJ, Zhang L, Lee CC, Schilkey FD, Sheth V, Woodward JE, Peckham HE, Schroth GP, Kim RW, Kingsmore SF. Sci Transl Med. 2011 Jan 12;3(65):65ra4.
February 15 - James Ford, MD
Genetic clues to treating pancreatic neuroendocrine tumors
Reference(s): DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N. Science. 2011 Jan 20. [Epub ahead of print]
Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. N Engl J Med. 2011 Feb 10;364(6):501-13.
Everolimus for advanced pancreatic neuroendocrine tumors. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. N Engl J Med. 2011
February 8 - Scott Seeley, MD, PhD
Cell biology meets Peutz Jeghers syndrome: organelle-based signaling in a heritable cancer syndrome
Reference(s): Christopher Boehlke et al. Primary cilia regulate mTORC1 activity and cell size through Lkb1. 2010 Nature Cell Biology
February 1 - Sarah Garcia, PhD
When Complex is Mendelian: the use of candidate exome sequencing to identify genetic contributors to impulsitivity.
Reference(s): A population-specific HTR2B stop codon predisposes to severe impulsivity. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S, Belmer A, Hodgkinson CA, Dell'osso L, Suvisaari J, Coccaro E, Rose RJ, Peltonen L, Virkkunen M, Goldman D. Nature. 2010 Dec 23;468(7327):1061-6. - PubMed PMID: 21179162
January 25 - Louanne Hudgins, MD
It’s a Mixed Bag: Mechanisms of mosaicism, chimerism, and uniparental disomy
Reference(s): Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Conlin LK, Thiel BD, Bonnemann CG, Medne L, Ernst LM, Zackai EH, Deardorff MA, Krantz ID, Hakonarson H, Spinner NB. Hum Mol Genet. 2010 Apr 1;19(7):1263-75. Epub 2010 Jan 6.
Chimerism resulting from parthenogenetic activation and dispermic fertilization. Winberg J, Gustavsson P, Lagerstedt-Robinson K, Blennow E, Lundin J, Iwarsson E, Nordenström A, Anderlid BM, Bondeson ML, Nordenskjöld A, Nordgren A. Am J Med Genet A. 2010 Sep;152A(9):2277-86.
January 18, 2011 - Stephanie Sottile
RAD51C in Fanconi anemia and breast/ovarian cancer susceptibility
Reference(s): Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V, Neveling K, Endt D, Kesterton I, Autore F, Fraternali F, Freund M, Hartmann L, Grimwade D, Roberts RG, Schaal H, Mohammed S, Rahman N, Schindler D, Mathew CG. Nat Genet. 2010 May;42(5):406-9. Epub 2010 Apr 18.PMID: 20400963
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, Freund M, Lichtner P, Hartmann L, Schaal H, Ramser J, Honisch E, Kubisch C, Wichmann HE, Kast K, Deissler H, Engel C, Müller-Myhsok B, Neveling K, Kiechle M, Mathew CG, Schindler D, Schmutzler RK, Hanenberg H. Nat Genet. 2010 May;42(5):410-4. Epub 2010 Apr 18.PMID: 20400964
January 11 - Neng Chen, MD
NextGen sequencing in molecular diagnosis
Reference(s): Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Haack TB, Danhauser K, Haberberger B, Hoser J, Strecker V, Boehm D, Uziel G, Lamantea E, Invernizzi F, Poulton J, Rolinski B, Iuso A, Biskup S, Schmidt T, Mewes HW, Wittig I, Meitinger T, Zeviani M, Prokisch H. Nat Genet. 2010 Dec;42(12):1131-4. Epub 2010 Nov 7.
January 4 - Gregory Enns, M.B. Ch.B
Mitochondrial sirtuins – novel therapeutic targets for redox-related disorders?
Reference(s): Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F, Chang Y. PLoS One. 2010;5(7):e11707. - PubMed PMID: 20661474
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Verdin E, Hirschey MD, Finley LW, Haigis MC. Trends Biochem Sci. 2010 Dec;35(12):669-75. Epub 2010 Sep 20. Review.
December 7 - Eric Muller II, MD, PhD
Genotype–phenotype correlation of two prevalent GJB2 mutations in chinese newborn infants ascertained from the Universal Newborn Hearing Screening Program
Reference(s): My Y et al. 2010. Genotype–phenotype correlation of two prevalent GJB2 mutations in chinese newborn infants ascertained from the Universal Newborn Hearing Screening Program. Am J Med Genet Part A. 152A:2912-2915.
Tang H-Y, et al. 2006. DNA sequence analysis of GJB2, encoding connexin 26: Observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. Am J Med Genet Part A 140A:2401–2415.
November 30 - Myla Ashfaq
WDR62 Mutations in Microcephaly and other Brain Malformations
Reference(s): Bilgüvar, K., Oztürk, A. K., Louvi, A., Kwan, K. Y., Choi, M., et al. (2010). Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature, 467(7312), 207-10. doi:10.1038/nature09327
Yu, T. W., Mochida, G. H., Tischfield, D. J., Sgaier, S. K., Flores-Sarnat, L. et al. (2010). Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. Nature Genetics 42(11), 1015–1020. doi:10.1038/ng.
November 16 - Kyla Dunn
A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy (FSHD)
Reference(s): Lemmers, R. J. L. F., van der Vliet, P. J., Klooster, R., Sacconi, S., Camaño, P., Dauwerse, J. G., Snider, L., et al. (2010). A unifying genetic model for facioscapulohumeral muscular dystrophy. Science, 329(5999), 1650-1653. doi:10.1126/science.1189044
Snider, L., Geng, L. N., Lemmers, R. J. L. F., Kyba, M., Ware, C. B., Nelson, A. M., Tawil, R., et al. (2010). Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene. PLoS Genet, 6(10), e1001181. doi:10.1371/journal.pgen.1001181
November 9 - Iris Schrijver, MD
Safety first: Next-generation prenatal diagnosis
Reference(s): Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Rossa W. K. Chiu, K. C. Allen Chan,Yuan Gao,Virginia Y. M. Lau,Wenli Zheng,Tak Y. Leung, Chris H. F. Foo,Bin Xie, Nancy B. Y. Tsui, Fiona M. F. Lun, Benny C. Y. Zee, Tze K. Lau, Charles R. Cantor, and Y. M. Dennis Lo. Proc Natl Acad Sci U S A. 2008 December 23; 105(51): 20458–20463
Analysis of the size distributions of fetal and maternal cell-free DNA by paired-end sequencing. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Clin Chem. 2010 Aug;56(8):1279-86.
November 2 - Lili Kuzmich
HDAC4 One Gene, Many Phenotypes
Reference(s): Haploinsufficiency of HDAC4 Causes Brachydactyly Mental Retardation Syndrome, with Brachydactyly Type E, Developmental Delays, and Behavioral Problems. Stephen R. Williams, Micheala A. Aldred, Vazken M. Der Kaloustian, Fahed Halal, Gordon Gowans, D. Ross McLeod, Sara Zondag, Helga V. Toriello, R. Ellen Magenis,and Sarah H. Elsea. The American Journal of Human Genetics August 2010, Vol. 87, pg: 219–228.
Array comparative genomic hybridisation of 52 subjects with a SmitheMagenis-like phenotype: identification of dosage sensitive loci also associated with schizophrenia, autism, and developmental delay. Stephen R Williams, Santhosh Girirajan, David Tegay, Norma Nowak,Eli Hatchwell, Sarah H Elsea. Journal of Medical Genetics April 2010,Vol. 47(4) pg:223-9.October 26 - Hank Greely, JD
October 26 - Hank Greely, JD
Genotyping as an Educational Tool – Some Thoughts
1. Various documents from Berkeley's DNA Testing program:
Flyer, Letter to students, Info sheets for students (2), Consent form
2. Council for Responsible Genetics Statement to the Assembly Higher Education Committee (Aug. 10, 2010)
3. Troy Duster, Welcome, Freshman. DNA Swabs, Please. Chron. Higher Ed. (May 28, 2010).
October 19 - Hannes Vogel, MD
Autism and Neuropathology
Reference(s): The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A, Chauhan V, Bobrowicz TW, de Leon M, Louis LA, Cohen IL, London E, Brown WT, Wisniewski T. Acta Neuropathol. 2010 Jun;119(6):755-70. - PubMed PMID: 20198484
Mapping early brain development in autism. Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J. Neuron. 2007 Oct 25;56(2):399-413. - PubMed PMID: 17964254
October 12 - Gemma Chandratillake
Kabuki Syndrome & MLL2
Reference(s): Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Nat Genet. 2010 Sep;42(9):790-3. - PubMed PMID: 20711175
October 5 - Dr. Olivera Mitrasinovic
When Informed Consent on Stored Biospecimens fails
(Panel discussion includes Law Professor Hank Greely and Dr. Uta Francke, former ASHG president)
Reference(s): The Havasupai Indian Tribe Case – lessons for research involving stored biologic samples. Mello mm, Wolf LE. N Engl. J. Med 2010 Jul; 363 (3):204-7. PMID 20538622
September 28 - Curt Scharfe, MD, PhD
The Challenges of Sequencing by Synthesis
Reference(s): The challenges of sequencing by synthesis. Fuller CW, Middendorf LR, Benner SA, Church GM, Harris T, Huang X, Jovanovich SB, Nelson JR, Schloss JA, Schwartz DC, Vezenov DV. Nat Biotechnol. 2009 Nov;27(11):1013-23. - PubMed PMID: 19898456
September 21 - Carlos Bustamante, PhD
The Characterization of Twenty Sequenced Human Genomes
Reference(s): The Characterization of Twenty Sequenced Human Genomes. Pelak K, Shianna KV, GE D, Maja JM, Zhu M. et al. PLos Genet 6 (9):e1001111. Doi.10.1371/journal.pgen.
June 5 - Melanie Manning, MD
Whole genome sequencing for everyone - are we ready?
Reference(s):
American Journal of Medical Genetics A 158A:1310-1319; Tabor et al.; "Informed consent for whole genome sequencing: a qualitative analysis of participant expectations and perceptions of risks, benefits and harms."
American Journal of Medical Genetics A 158A: AJMG Sequence: "At $1,000, is genomic sequencing clinically useful in newborns?"
JAMA 307:461-462; Goldenberg and Sharp; "The ethical hazards and programmatic challenges of genomic newborn screening"
May 22 - Andrea Kwan, MS, LCGC
GPS-guided understanding of KAT6B -associated phenotypes
Reference(s):
Am J Hum Genet. 2012 Feb 10;90(2):282-9. Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome. Campeau PM, Kim JC, Lu JT, Schwartzentruber JA, Abdul-Rahman OA, Schlaubitz S, Murdock DM, Jiang MM, Lammer EJ, Enns GM, Rhead WJ, Rowland J, Robertson SP, Cormier-Daire V, Bainbridge MN, Yang XJ, Gingras MC, Gibbs RA, Rosenblatt DS, Majewski J, Lee BH.
Am J Hum Genet. 2012 Feb 10;90(2):290-4. De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome. Simpson MA, Deshpande C, Dafou D, Vissers LE, Woollard WJ, Holder SE, Gillessen-Kaesbach G, Derks R, White SM, Cohen-Snuijf R, Kant SG, Hoefsloot LH, Reardon W, Brunner HG, Bongers EM, Trembath RC.
May 8 - Jonathan Bernstein, MD, PhD
Not what we expected to see in the mirror: RAD51 implicated in congenital mirror movements: RAD51 haploinsufficiency causes congenital mirror movements in humans
Reference(s): RAD51 haploinsufficiency causes congenital mirror movements in humans. Depienne C, Bouteiller D, Méneret A, Billot S, Groppa S, Klebe S, Charbonnier-Beaupel F, Corvol JC, Saraiva JP, Brueggemann N, Bhatia K, Cincotta M, Brochard V, Flamand-Roze C, Carpentier W, Meunier S, Marie Y, Gaussen M, Stevanin G, Wehrle R, Vidailhet M, Klein C, Dusart I, Brice A, Roze E. Am J Hum Genet. 2012 Feb 10;90(2):301-7. Epub 2012 Feb 2.
May 1 - Marie-Luise Brennan, MD, PhD
Angelman syndrome: genotype-phenotype studies on more than just deletions
Reference(s): Tan WH, et al., Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan;155A(1):81-90. doi: 10.1002/ajmg.a.33775. PubMed PMID: 21204213.
April 24 - Tina Cowan, MD
Nitric oxide and the pathophysiology of mitochondrial disease
April 17 - Layla Shahmirzadi
Non-Invasive Prenatal Diagnosis: A comparison of validations studies
Reference(s): Palomaki GE et al. (2011) DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genetics in Medicine, 13(11): 913-920.
Palomaki GE et al. (2012) DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genetics in Medicine, 14:296-305.
Bianchi DW et al. (2012) Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstetrics & Gynecology, 119(5) 1-12.
April 10 - Hinco Gierman, PhD
How mutations make us sick: Loss-of-function variants in the human genome & the implications for personalized medicine
Reference(s): A systematic survey of loss-of-function variants in human protein-coding genes. MacArthur DG, Balasubramanian S, Frankish A, Huang N, Morris J, Walter K, Jostins L, Habegger L, Pickrell JK, Montgomery SB, Albers CA, Zhang ZD, Conrad DF, Lunter G, Zheng H, Ayub Q, DePristo MA, Banks E, Hu M, Handsaker RE, Rosenfeld JA, Fromer M, Jin M, Mu XJ, Khurana E, Ye K, Kay M, Saunders GI, Suner MM, Hunt T, Barnes IH, Amid C, Carvalho-Silva DR, Bignell AH, Snow C, Yngvadottir B, Bumpstead S, Cooper DN, Xue Y, Romero IG; 1000 Genomes Project Consortium, Wang J, Li Y, Gibbs RA, McCarroll SA, Dermitzakis ET, Pritchard JK, Barrett JC, Harrow J, Hurles ME, Gerstein MB, Tyler-Smith C. Science. 2012 Feb 17;335(6070):823-8.
April 3 - Bita Nehoray
Kalydeco: A Cure for Cystic Fibrosis?
Reference(s): Ivacaftor in Subjects with Cystic Fibrosis who are Homozygous for the F508del-CFTR Mutation. Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordoñez CL, Geller DE; for the VX08-770-104 Study Group.
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group.
March 20 - Aarin Ables
Systemic Lupus Erythematosus Susceptibility: Identification by GWAS
Reference(s): Lessard CJ, Adrianto I, Kelly JA et al. Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study. Am J Hum Genet 2011;88:83–91.
Graham RR, Cotsapas C, Davies L et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 2008;40:1059-61.
Jarvinen TM, Hellquist A, Zucchelli1 M et al. Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. Rheumatology 2012;51:87-92
March 13 - Hua Tang, PhD
Confounding due to population stratification: common vs rare variants
Reference(s): Differential confounding of rare and common variants in spatially structured populations. Mathieson I, McVean G. Nat Genet. 2012 Mar;44(3):243-6. - PubMed PMID: 22306651
March 6 - Megan Grove
The Heart of the Matter: Myopalladin Mutations and Clinical Heterogeneity in Inherited Cardiomyopathies
Reference(s): Purevjav E, Arimura T, Augustin S, Huby AC, Takagi K, Nunoda S, Kearney DL, Taylor MD, Terasaki F, Bos JM, Ommen SR, Shibata H, Takahashi M, Itoh-Satoh M, McKenna WJ, Murphy RT, Labeit S, Yamanaka Y, Machida N, Park JE, Alexander PM, Weintraub RG, Kitaura Y, Ackerman MJ, Kimura A, Towbin JA. Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations. Hum Mol Genet. 2012 Feb 14. [Epub ahead of print]
Duboscq-Bidot L, Xu P, Charron P, Neyroud N, Dilanian G, Millaire A, Bors V, Komajda M, Villard E. Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy.Cardiovasc Res. 2008 Jan;77(1):118-2
February 28 - Joachim Hallymayer, MD
The Emperor’s New Clothes – IQ and GWAS
Reference(s): Deary IJ, Yang J, Davies G, Harris SE, Tenesa A, Liewald D, Luciano M, Lopez LM, Gow AJ, Corley J, Redmond P, Fox HC, Rowe SJ, Haggarty P, McNeill G, Goddard ME, Porteous DJ, Whalley LJ, Starr JM, Visscher PM. Genetic contributions to stability and change in intelligence from childhood to old age. Nature. 2012 Jan 18;482(7384):212-5
Davies G, Tenesa A, Payton A, Yang J, Harris SE, Liewald D, Ke X, Le Hellard S, Christoforou A, Luciano M, McGhee K, Lopez L, Gow AJ, Corley J, Redmond P, Fox HC, Haggarty P, Whalley LJ, McNeill G, Goddard ME, Espeseth T, Lundervold AJ, Reinvang I, Pickles A, Steen VM, Ollier W, Porteous DJ, Horan M, Starr JM, Pendleton N, Visscher PM, Deary IJ. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry. 2011 Oct;16(10):996-1005.
February 21 - Emily Hurford
TRPV4 and associated phenotypes: Charcot-Marie-Tooth, arthropathy, and skeletal dysplasias
Reference(s): C.J. Klein, Y. Shi, F. Fecto, et al. (2011). TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies. Neurology, 76, 887-894.
Lamande, S.R., Yuan, Y, Irma, L.G., et al. (2011). Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nature Genetics, 43(11), 1142-1146.
Andreucci, E., Aftimos, S., Alcausin, M., et al. (2011). TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted by clinical, radiographic, and molecular studies in 21 new families. Orphanet Journal of Rare Diseases; 6(37).
February 14 - Jim Ford, MD
DICER1 Mutations Cancer: Tumor Suppressor Gene or Oncogene?
February 7 - Angela Myers, MD
RASopathies: do they share perinatal features?
Reference(s): Baldassarre, G. et al. Prenatal features of Noonan syndrome: prevalence and prognostic value. Prenatal Diagnosis 31, 949-954 (2011)
Bakker, M., Pajkrt, E., Mathijssen, I.B. & Bilardo, C.M. Targeted ultrasound examination and DNA testing for Noonan syndrome, in fetuses with increased nuchal translucency and normal karyotype. Prenatal Diagnosis 31, 833-840 (2011)
Digilio, M.C. et al. RASopathies: Clinical Diagnosis in the First Year of Life. Molecular Syndromology 1, 282-289 (2010)
January 31 - Angela Arredondo, MD
Breathing new life into PHOX2B and it's role in congenital central hypoventilation syndrome
Reference(s): A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM. Nature. 2012 Jan 26;481(7382):463-8. - PubMed PMID: 22237023
January 24 - Louanne Hudgins, MD
Are the autoimmune disease susceptibility disorders (AIS) distinct entities?
Reference(s): Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. Jin Y, Birlea SA, Fain PR, Gowan K, Riccardi SL, Holland PJ, Mailloux CM, Sufit AJ, Hutton SM, Amadi-Myers A, Bennett DC, Wallace MR, McCormack WT, Kemp EH, Gawkrodger DJ, Weetman AP, Picardo M, Leone G, Taïeb A, Jouary T, Ezzedine K, van Geel N, Lambert J, Overbeck A, Spritz RA. N Engl J Med. 2010 May 6;362(18):1686-97.
NALP1 in vitiligo-associated multiple autoimmune disease. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G, Bennett DC, Fain PR, Spritz RA. N Engl J Med. 2007 Mar 22;356(12):1216-25.
January 17 - Hannes Vogel, MD
Run, don’t walk to this HGJC!
January 10 - Gregory Enns, MB ChB
Exercise and eat dark chocolate – the Willy Wonka approach to improving mitochondrial function.
Reference(s): (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal FJ, Hogan MC, Malek MH. J Physiol. 2011 Sep 15;589(Pt 18):4615-31. - PubMed PMID: 21788351
Cocoa and chocolate in human health and disease. Katz DL, Doughty K, Ali A. Antioxid Redox Signal. 2011 Nov 15;15(10):2779-811. - PubMed PMID: 21470061
December 13 - Yael Wilnai, MD
Clinical significance of copy number variants in intellectual and developmental disabilities
Reference(s): An evidence-based apprach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med 2011:13(9):777-784
A copy number variation morbidity map of developmental delay. Nature Genetics 2011:43(9): 838-848
December 6 - Edward Esplin, MD, PhD
APC: Texas Two-Step vs the Two Hit hypothesis
November 29 - Anna-Kaisa Niemi, MD,PhD
CMAMMA solved. What's next - CPAPPA?
Reference(s): Sloan et al. 2011. Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria (CMAMMA). Nat Genet. 2011 43:883-6. PMID: 21841779.
November 15 - Jessica Profato
RAD51C: Investigations of a Potential Breast and Ovarian Cancer Susceptibility Gene
Reference(s): Vuorela M, Pylkäs K, Hartikainen JM, Sundfeldt K, Lindblom A, von Wachenfeldt Wäppling A, Haanpää M, Puistola U, Rosengren A, Anttila M, Kosma VM, Mannermaa A, Winqvist R. 2011. Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility. Breast Cancer Res Treat. Jul 13. [Epub ahead of print]
Pelttari LM, Heikkinen T, Thompson D, Kallioniemi A, Schleutker J, Holli K, Blomqvist C, Aittomäki K, Bützow R, Nevanlinna H. 2011. RAD51C is a susceptibility gene for ovarian cancer. Hum Mol Genet. Aug 15;20(16):3278-88. Epub 2011 May 25.
November 8 - Nadine Rayes
Uniparental disomy detection by SNP microarray analysis
Reference(s): Papenhausen, et al. UPD detection using homozygosity profiling with a SNP genotyping microarray. Am J Med Genet A. 2011
Conlin, et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet. 2010
November 1 - Curt Scharfe, MD
Illuminating mitochondrial calcium uptake
Reference(s): MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK. Nature. 2010 Sep 16;467(7313):291-6. - PubMed PMID: 20693986
Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK. Nature. 2011 Aug 18;476(7360):341-5. - PubMed PMID: 21685886
October 25 - Hank Greely, JD
End of Sex
Reference(s): Hayashi et al., Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells, Cell (2011), doi:10.1016/j.cell.2011.06.052
October 18 - Hui Wang, PhD
GWA study in the Pre-sequencing Era
Reference(s): Holm H, Gudbjartsson DF, et. al. (2011) A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nat Genet. 43(4):316-20.
October 11 - Theresa Boyle, MD, PhD
Genetics of Type 1 Diabetes
Reference(s): Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem. 2011 Feb;57(2):176-85. Epub 2011 Jan 4. Review. PubMed PMID: 21205883.
Forlenza GP, Rewers M. The epidemic of type 1 diabetes: what is it telling us? Curr Opin Endocrinol Diabetes Obes. 2011 Aug;18(4):248-51. PubMed PMID: 21844707.
Baschal EE, Sarkar SA, Boyle TA, Siebert JC, Jasinski JM, Grabek KR, Armstrong TK, Babu SR, Fain PR, Steck AK, Rewers MJ, Eisenbarth GS. Replication and further characterization of a Type 1 diabetes-associated locus at the telomeric end of the major histocompatibility complex. J Diabetes. 2011 Sep;3(3):238-47. doi: 10.1111/j.1753-0407.2011.00131.x. PubMed PMID: 21631897.
October 4 - Carlos Bustamante, PhD
Bayesian inference of ancient human demography from individual genome sequences
Reference(s): Bayesian inference of ancient human demography from individual genome sequences. Gronau I, Hubisz MJ, Gulko B, Danko CG, Siepel A. Nat Genet. 2011 Sep 18. doi: 10.1038/ng.937. [Epub ahead of print]
June 5 - Melanie Manning, MD
Of Mice and Men, a Down Syndrome Potpourri
Reference(s): Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Velazquez R, Ash JA, Powers BE, Kelley CM, Strawderman M, Luscher ZI, Ginsberg SD, Mufson EJ, Strupp BJ. Neurobiol Dis. 2013 Apr 30 - PubMed PMID: 23643842
Contributions of a specialty clinic for children and adolescents with Down syndrome. Skotko BG, Davidson EJ, Weintraub GS. Am J Med Genet A. 2013 Mar;161(3):430-7. - PubMed PMID: 23401090
Prenatal treatment prevents learning deficit in Down syndrome model. Incerti M, Horowitz K, Roberson R, Abebe D, Toso L, Caballero M, Spong CY. PLoS One. 2012;7(11):e50724. - PubMed PMID: 23209818
May 29 - Iris Schrijver, MD
Chronic Lymphocytic Leukemina: Progress for Progression
Reference(s): MiR-181b: new perspective to evaluate disease progression in chronic lymphocytic leukemia. Visone R, Veronese A, Balatti V, Croce CM.
Oncotarget. 2012 Feb;3(2):195-202. - PubMed PMID: 22350310
Date: May 22 - Jon Bernstein, MD, PhD
Somatic genetic events explain the distribution of cutaneous findings in Sturge-Weber Syndrome and Familial Glomovenous Malformations
Reference(s): Sturge-Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. N Engl J Med. 2013 May 8 - PubMed PMID: 23656586
Somatic uniparental isodisomy explains multifocality of glomuvenous malformations. Amyere M, Aerts V, Brouillard P, McIntyre BA, Duhoux FP, Wassef M, Enjolras O, Mulliken JB, Devuyst O, Antoine-Poirel H, Boon LM, Vikkula M. Am J Hum Genet. 2013 Feb 7;92(2):188-96. - PubMed PMID: 23375657
May 15 - Joachim Hallmayer, MD
Neurexin, self chains, and neurodevelopmental disorders
Reference(s): Molecular analysis of a deletion hotspot in the NRXN1 region reveals the involvement of short inverted repeats in deletion CNVs. Chen X, Shen Y, Zhang F, Chiang C, Pillalamarri V, Blumenthal I, Talkowski M, Wu BL, Gusella JF. Am J Hum Genet. 2013 Mar 7;92(3):375-86. - PubMed PMID: 23472757
Increased genome instability in human DNA segments with self-chains: homology-induced structural variations via replicative mechanisms. Zhou W, Zhang F, Chen X, Shen Y, Lupski JR, Jin L. Hum Mol Genet. 2013 Mar 15 - PubMed PMID: 23474816
May 8 - Edward Esplin, MD, PhD
To benign, or not to benign: answering the question...
Reference(s): Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D. Hum Mutat. 2012 Aug;33(8):1228-38. - PubMed PMID: 22505045
May 1 - Julien Couthouis, PhD
Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy
Reference(s): Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, McDonald K, Stajich JM, Mahjneh I, Vihola A, Raheem O, Penttilä S, Lehtinen S, Huovinen S, Palmio J, Tasca G, Ricci E, Hackman P, Hauser M, Katsanis N, Udd B. Nat Genet. 2012 Apr;44(4):450-5, S1-2. - PubMed PMID: 22366786
Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Harms MB, Sommerville RB, Allred P, Bell S, Ma D, Cooper P, Lopate G, Pestronk A, Weihl CC, Baloh RH. Ann Neurol. 2012 Mar;71(3):407-16. - PubMed PMID: 22334415
DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions. Sato T, Hayashi YK, Oya Y, Kondo T, Sugie K, Kaneda D, Houzen H, Yabe I, Sasaki H, Noguchi S, Nonaka I, Osawa M, Nishino I. Neuromuscul Disord. 2013 Mar;23(3):269-76. - PubMed PMID: 23394708
April 24 - Curt Scharfe, MD
The search for genetic causes of rare disorders of copper metabolism
Reference(s): Application of exome sequencing in the search for genetic causes of rare disorders of copper metabolism. Fuchs SA, Harakalova M, van Haaften G, van Hasselt PM, Cuppen E, Houwen RH. Metallomics. 2012 Jul;4(7):606-13. doi: 10.1039/c2mt20034a. Epub 2012 May 4.
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D. Hum Mutat. 2012 Aug;33(8):1228-38. - PubMed PMID: 22505045
April 17 - Yael Wilnai, MD
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
Reference(s): Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Nat Med. 2013 Apr 7 - PubMed PMID: 23563705
April 10 - Gregory Kellogg, BS
Hemizygous mutations on undeleted chromosome: A cause of variability in 22q11.2 deletion syndrome
Reference(s): Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS. McDonald-McGinn DM, Fahiminiya S,Revil Tée, et al. J Med Genet 2013;50:80–90.
April 3 - Louanne Hudgins, MD, FACMG
aCGH in Prenatal Diagnosis: What do we gain?
Reference(s): Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis. Ronald J. Wapner, M.D., Christa Lese Martin, Ph.D., Brynn Levy, M.Sc.(Med.), Ph.D., Blake C. Ballif, Ph.D., Christine M. Eng, M.D., Julia M. Zachary, Melissa Savage, M.S., Lawrence D. Platt, M.D., Daniel Saltzman, M.D., William A. Grobman, M.D., M.B.A., Susan Klugman, M.D., Thomas Scholl, Ph.D., Joe Leigh Simpson, M.D., Kimberly McCall, B.S., Vimla S. Aggarwal, M.B., B.S., Brian Bunke, B.S., Odelia Nahum, M.Sc., Ankita Patel, Ph.D., Allen N. Lamb, Ph.D., Elizabeth A. Thom, Ph.D., Arthur L. Beaudet, M.D., David H. Ledbetter, Ph.D., Lisa G. Shaffer, Ph.D., and Laird Jackson, M.D. N Engl J Med 2012; 367:2175-2184December 6, 2012DOI: 10.1056/NEJMoa1203382
March 13 - Kitch Wilson, MD, PhD
A technical reason why next generation sequencing may not be the answer to everything
Reference(s): Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Kirby A, Gnirke A, Jaffe DB, Barešová V, Pochet N, Blumenstiel B, Ye C, Aird D, Stevens C, Robinson JT, Cabili MN, Gat-Viks I, Kelliher E, Daza R, Defelice M, Hůlková H, Sovová J, Vylet'al P, Antignac C, Guttman M, Handsaker RE, Perrin D, Steelman S, Sigurdsson S, Scheinman SJ, Sougnez C, Cibulskis K, Parkin M, Green T, Rossin E, Zody MC, Xavier RJ, Pollak MR, Alper SL, Lindblad-Toh K, Gabriel S, Hart PS, Regev A, Nusbaum C, Kmoch S, Bleyer AJ, Lander ES, Daly MJ. Nat Genet. 2013 Mar;45(3) - PubMed PMID: 23396133
March 6 - Andrea Kwan, MS, LCGC
Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans
Reference(s): Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans. de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, Van Haeringen A, Geneviève D, Goldenberg A, Oufadem M, Manouvrier S, Munnich A, Vidigal JA, Vekemans M, Lyonnet S, Henrion-Caude A, Ventura A, Amiel J. Nat Genet. 2011 Sep 4;43(10):1026-30. doi: 10.1038/ng.915.
February 27 - Sahil Kejriwal, BS
The Cardiomyopathy Variant Conundrum
Reference(s): New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, Sajadieh A, Haunsø S, Svendsen JH, Olesen MS, (2013). New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. [Epub ahead of print]
February 20 - Kelly E. Ormond, MS, LCGC
An informatics approach to analyzing the incidentalome
Reference(s): An informatics approach to analyzing the incidentalome. Jonathan S. Berg MD, PhD, Michael Adams MS, Nassib Nassar PhD, Chris Bizon PhD, Kristy Lee MS, Charles P. Schmitt PhD, Kirk C. Wilhelmsen MD, PhD & James P. Evans MD, PhD. Genetics in Medicine (2013) 15, 36–44 doi:10.1038/gim.2012.112 Received 17 July 2012 Accepted 27 July 2012 Published online 20 September 2012
February 13 - Amirah Khouzam, MA
TREM2 Variants in Alzheimer's Disease
Reference(s): TREM2 Variants in Alzheimer's Disease. Rita Guerreiro, Ph.D., Aleksandra Wojtas, M.S., Jose Bras, Ph.D., Minerva Carrasquillo, Ph.D., Ekaterina Rogaeva, Ph.D., Elisa Majounie, Ph.D., Carlos Cruchaga, Ph.D., Celeste Sassi, M.D., John S.K. Kauwe, Ph.D., Steven Younkin, M.D., Ph.D., Lilinaz Hazrati, M.D., Ph.D., John Collinge, M.D., Jennifer Pocock, Ph.D., Tammaryn Lashley, Ph.D., Julie Williams, Ph.D., Jean-Charles Lambert, Ph.D., Philippe Amouyel, M.D., Ph.D., Alison Goate, Ph.D., Rosa Rademakers, Ph.D., Kevin Morgan, Ph.D., John Powell, Ph.D., Peter St. George-Hyslop, M.D., Andrew Singleton, Ph.D., and John Hardy, Ph.D. for the Alzheimer Genetic Analysis Group. N Engl J Med 2013; 368:117-127January 10, 2013DOI: 10.1056/NEJMoa1211851
February 6 - Rachel Farrell, BA
Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan
Reference(s): Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Roscioli T, Kamsteeg EJ, Buysse K, Maystadt I, van Reeuwijk J, van den Elzen C, van Beusekom E, Riemersma M, Pfundt R, Vissers LE, Schraders M, Altunoglu U, Buckley MF, Brunner HG, Grisart B, Zhou H, Veltman JA, Gilissen C, Mancini GM, Delrée P, Willemsen MA, Ramadža DP, Chitayat D, Bennett C, Sheridan E, Peeters EA, Tan-Sindhunata GM, de Die-Smulders CE, Devriendt K, Kayserili H, El-Hashash OA, Stemple DL, Lefeber DJ, Lin YY, van Bokhoven H. Nat Genet. 2012 May;44(5) - PubMed PMID: 22522421
January 30 - Justin Odegaard, MD, PhD
Rate of de novo mutations and the importance of father’s age to disease risk
Reference(s): Rate of de novo mutations and the importance of father's age to disease risk.
Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Jonasdottir A, Wong WS, Sigurdsson G, Walters GB, Steinberg S, Helgason H, Thorleifsson G, Gudbjartsson DF, Helgason A, Magnusson OT, Thorsteinsdottir U, Stefansson K. Nature. 2012 Aug 23;488(7412) - PubMed PMID: 22914163
January 23 - Emily Hendricks, BA
Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development
Reference(s): Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development.
Arboleda V, Lee H, Sánchez F, Délot E, Sandberg D, Grody W, Nelson S, Vilain E.
Clin Genet. 2013 Jan;83(1) - PubMed PMID: 22435390
January 16 - Gregory Enns, MB ChB
Brain mitochondrial glutathione transport – a link to neurodegeneration
Reference(s): Mitochondrial Glutathione Transport is a Key Determinant of Neuronal Susceptibility to Oxidative and Nitrosative Stress. Wilkins HM, Kirchhof D, Manning E, Joseph JW, Linseman DA. J Biol Chem. 2013 Jan 2. [Epub ahead of print]
January 9 - Hui Wang, PhD
Predict DNA from RNA: a New Data Security Issue?
Reference(s): Bayesian method to predict individual SNP genotypes from gene expression data. Schadt EE, Woo S, Hao K. Nat Genet. 2012 May; 44(5):603-8. doi: 10.1038/ng.2248.
December 5 - Adrienne Miller, BA
Examining the impact of ICE in human development
Reference(s): Alfarawati S, Fragouli E, Colls P, Wells D (2012). Embryos of Robertsonian Translocation Carriers Exhibit a Mitotic Interchromosomal Effect That Enhances Genetic Instability during Early Development. PLoS Genet 8(10): e1003025. doi:10.1371/journal.pgen.1003025
November 28 - Paldeep Atwal, MB ChB
Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants
Reference(s):
Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants. Santhosh Girirajan, M.B., B.S., Ph.D., Jill A. Rosenfeld, M.S., Bradley P. Coe, Ph.D., Sumit Parikh, M.D., Neil Friedman, M.B., Ch.B., Amy Goldstein, M.D., Robyn A. Filipink, M.D., Juliann S. McConnell, M.S., Brad Angle, M.D., Wendy S. Meschino, M.D., Marjan M. Nezarati, M.D., Alexander Asamoah, M.D., Kelly E. Jackson, M.S., Gordon C. Gowans, M.D., Judith A. Martin, M.D., Erin P. Carmany, M.S., David W. Stockton, M.D., Rhonda E. Schnur, M.D., Lynette S. Penney, M.D., Donna M. Martin, M.D., Ph.D., Salmo Raskin, Ph.D., Kathleen Leppig, M.D., Heidi Thiese, M.S., Rosemarie Smith, M.D., Erika Aberg, M.S., Dmitriy M. Niyazov, M.D., Luis F. Escobar, M.D., Dima El-Khechen, M.S., Kisha D. Johnson, M.S., Robert R. Lebel, M.D., Kiana Siefkas, M.S., Susie Ball, M.S., Natasha Shur, M.D., Marianne McGuire, M.S., Campbell K. Brasington, M.S., J. Edward Spence, M.D., Laura S. Martin, M.D., Carol Clericuzio, M.D., Blake C. Ballif, Ph.D., Lisa G. Shaffer, Ph.D., and Evan E. Eichler, Ph.D. N Engl J Med 2012; 367:1321-1331October 4, 2012DOI: 10.1056/NEJMoa1200395
November 14 - Kristen Dilzell, BS
Common Breast Cancer Risk Variants: Are they useful in clinical practice and management?
Reference(s): A Role for Common Genomic Variants in the Assessment of Familial Breast Cancer. J Clin Oncol. 2012 Oct 29. [Epub ahead of print]
October 31 - Marie-Luise Brennan, MD, PhD
Colon Cancer: PIK3CA mutation, aspirin therapy and survival
Reference(s): Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival. N Engl J Med. 2012 Oct 25;367(17):1596-606.
October 17 - Hinco Gierman, PhD
Clinical applications of Exome and Whole Genome Sequencing
Reference(s): Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, Humphray S, Saffrey P, Kingsbury Z, Weir JC, Betley J, Grocock RJ, Margulies EH, Farrow EG, Artman M, Safina NP, Petrikin JE, Hall KP, Kingsmore SF. Sci Transl Med. 2012 Oct 3;4(154):154ra135. doi: 10.1126/scitranslmed.3004041
Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability. de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Silfhout AT, Koolen DA, de Vries P, Gilissen C, Del Rosario M, Hoischen A, Scheffer H, de Vries BB, Brunner HG, Veltman JA, Vissers LE. N Engl J Med. 2012 Oct 3
October 10 - Michael Niaki, MD
Copy Number of DUF1220 Predicts Brain Size: What is your copy number?
Reference(s): DUF1220-Domain Copy Number Implicated in Human Brain-Size Pathology and Evolution. Dumas LJ, O'Bleness MS, Davis JM, Dickens CM, Anderson N, Keeney JG, Jackson J, Sikela M, Raznahan A, Giedd J, Rapoport J, Nagamani SS, Erez A, Brunetti-Pierri N, Sugalski R, Lupski JR, Fingerlin T, Cheung SW, Sikela JM. Am J Hum Genet. 2012 Sep 7;91(3):444-54. - PubMed PMID: 22901949
October 3 -Lee Kozar
Decoding the ENCODE Database
Reference(s): An integrated encyclopedia of DNA elements in the human genome. The ENCODE Project Consortium. Nature, 489, 57–74(06 September 2012).
September 26 - Hank Greely, JD
On De-Extinction: Should Genetics Be Used To Revive Extinct Species?
Reference(s):
For an overview of some of the thinking and activities, see the website for Revive and Restore: http://rare.longnow.org .
For the only article I know that goes into any of the legal and ethical issues (though I don't think its technical solution is likely), see this piece from 2000: Corey A. Salsberg, Resurrecting the Woolly Mammoth: Science, Law, Ethics, and Religion, 2000 Stan. Tech. L. Rev. 1. (http://stlr.stanford.edu/2000/03/resurrecting-the-woolly-mammoth/ )
June 4 - Tina Cowan, PhD
Beyond the Urea Cycle: A New Disorder of Ureagenesis
van Karnebeek CD, Sly WS, Ross CJ, Salvarinova R, Yaplito-Lee J, Santra S, Shyr C, Horvath GA, Eydoux P, Lehman AM, Bernard V, Newlove T, Ukpeh H, Chakrapani A, Preece MA, Ball S, Pitt J, Vallance HD, Coulter-Mackie M, Nguyen H, Zhang LH, Bhavsar AP, Sinclair G, Waheed A, Wasserman WW, Stockler-Ipsiroglu S.
Am J Hum Genet. 2014 Mar 6;94(3):453-61. - PubMed PMID: 24530203
May 28 - Paldeep Atwal, MB ChB
Carnitine: Lessons From A Nationwide Screening Program
Rasmussen J, Nielsen OW, Janzen N, Duno M, Køber L, Steuerwald U, Lund AM.
J Inherit Metab Dis. 2014 Mar;37(2):215-22. - PubMed PMID: 23653224
May 14 - Kelly E. Ormond, MS, LCGC
Incidental sequencing findings in kids: let the debate rage on!
Reference(s): Addressing the ethical challenges in genetic testing and sequencing of children.
Clayton EW, McCullough LB, Biesecker LG, Joffe S, Ross LF, Wolf SM; Clinical Sequencing Exploratory Research (CSER) Consortium Pediatrics Working Group.
Am J Bioeth. 2014 Mar;14(3):3-9. - PubMed PMID: 24592828
May 7 - Iris Schrijver, MD
Expecting the unexpected: Discordant noninvasive prenatal testing
Reference(s): Discordant noninvasive prenatal testing results in a patient subsequently diagnosed with metastatic disease. Osborne CM, Hardisty E, Devers P, Kaiser-Rogers K, Hayden MA, Goodnight W, Vora NL. Prenat Diagn. 2013 Jun;33(6):609-11. - PubMed PMID: 23559449
Background Material:
Commercial landscape of noninvasive prenatal testing in the United States.
Agarwal A, Sayres LC, Cho MK, Cook-Deegan R, Chandrasekharan S.
Prenat Diagn. 2013 Jun;33(6):521-31. - PubMed PMID: 23686656
April 30 - Curt Scharfe, MD, PhD
PhenoTips: patient phenotyping software for clinical and research use
Reference(s): PhenoTips: patient phenotyping software for clinical and research use. Girdea M, Dumitriu S, Fiume M, Bowdin S, Boycott KM, Chénier S, Chitayat D, Faghfoury H, Meyn MS, Ray PN, So J, Stavropoulos DJ, Brudno M.Hum Mutat. 2013 Aug;34(8):1057-65. - PubMed PMID: 23636887
April 23 - Joanne Taylor, MS, LCGC
The Importance of Comprehensive Chromosome Screening Prior to In Vitro Fertilization
Reference(s): The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, Scott RT. Fertil Steril. 2014 Mar;101(3):656-663.e1. - PubMed PMID: 24355045
Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Scott RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Fertil Steril. 2013 Sep;100(3):697-703. - PubMed PMID: 23731996
April 9 - Michael Niaki, MD
Recent mitochondrial research on targeted zinc fingers
Reference(s): Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. Gammage PA, Rorbach J, Vincent AI, Rebar EJ, Minczuk M. EMBO Mol Med. 2014 Apr 1;6(4):458-66. - PubMed PMID: 24567072
Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease. Bacman SR, Williams SL, Garcia S, Moraes CT. Gene Ther. 2010 Jun;17(6):713-20. - PubMed PMID: 20220783
Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Bacman SR, Williams SL, Pinto M, Peralta S, Moraes CT. Nat Med. 2013 Sep;19(9):1111-3. - PubMed PMID: 23913125
April 2 - Louanne Hudgins, MD
EFTUD2: The Great Masquerader
Reference(s): Hum Mutat. 2014 Apr;35(4):478-85. doi: 10.1002/humu.22517. Epub 2014 Mar 5.
Delineation of EFTUD2 Haploinsufficiency-Related Phenotypes Through a Series of 36 Patients. Lehalle D1, Gordon CT, Oufadem M, Goudefroye G, Boutaud L, Alessandri JL, Baena N, Baujat G, Baumann C, Boute-Benejean O, Caumes R, Decaestecker C, Gaillard D, Goldenberg A, Gonzales M, Holder-Espinasse M, Jacquemont ML, Lacombe D, Manouvrier-Hanu S, Marlin S, Mathieu-Dramard M, Morin G,Pasquier L, Petit F, Rio M, Smigiel R, Thauvin-Robinet C, Vasiljevic A, Verloes A, Malan V, Munnich A, de Pontual L, Vekemans M, Lyonnet S, Attié-Bitach T,Amiel J.
March 12 - Martina Lefterova, MD, PhD
DNA sequencing versus standard prenatal aneuploidy screening
Reference(s): DNA sequencing versus standard prenatal aneuploidy screening. Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, Craig JA, Chudova DI, Devers PL, Jones KW, Oliver K, Rava RP, Sehnert AJ; CARE Study Group. N Engl J Med. 2014 Feb 27;370(9):799-808. - PubMed PMID: 24571752
March 5 - Kerry Kingham, MS, LCGC
PALB2, clinical implications
Reference(s): Comprehensive sequencing of PALB2 in patients with breast cancer suggests PALB2 mutations explain a subset of hereditary breast cancer. Fernandes PH, Saam J, Peterson J, Hughes E, Kaldate R, Cummings S, Theisen A, Chen S, Trost J, Roa BB. Cancer. 2014 Jan 10 - PubMed PMID: 24415441
February 26 - Swaroop Aradhya, PhD, FACMG
Dynamic genomes: somatic mosaicism in humans
Reference(s): Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10 362 consecutive cases. Pham J, Shaw C, Pursley A, Hixson P, Sampath S, Roney E, Gambin T, Kang SH, Bi W, Lalani S, Bacino C, Lupski JR, Stankiewicz P, Patel A, Cheung SW. Eur J Hum Genet. 2014 Jan 8 - PubMed PMID: 24398791
Genetics. Genome mosaicism--one human, multiple genomes. Lupski JR. Science. 2013 Jul 26;341(6144):358-9. - PubMed PMID: 23888031
February 19, 2014 - Yael Wilnai, MD
3-Methylglutaconic aciduria—lessons from 50 genes and 977 patients
Reference(s): 3-Methylglutaconic aciduria--lessons from 50 genes and 977 patients Wortmann SB, Kluijtmans LA, Rodenburg RJ, Sass JO, Nouws J, van Kaauwen EP, Kleefstra T, Tranebjaerg L, de Vries MC, Isohanni P, Walter K, Alkuraya FS, Smuts I, Reinecke CJ, van der Westhuizen FH, Thorburn D, Smeitink JA, Morava E, Wevers RA. J Inherit Metab Dis. 2013 Nov;36(6):913-21. - PubMed PMID: 23355087
February 12 - Natalia Gomez-Ospina, MD, PhD
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy
Reference(s): Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy Alessandra Biffi, Eugenio Montini, Laura Lorioli, Martina Cesani, Francesca Fumagalli, Tiziana Plati, Cristina Baldoli, Sabata Martino, Andrea Calabria, Sabrina Canale, Fabrizio Benedicenti, Giuliana Vallanti, Luca Biasco, Simone Leo, Nabil Kabbara, Gianluigi Zanetti, William B. Rizzo, Nalini A. L. Mehta, Maria Pia Cicalese, Miriam Casiraghi, Jaap J. Boelens, Ubaldo Del Carro, David J. Dow, Manfred Schmidt, Andrea Assanelli, Victor Neduva, Clelia Di Serio, Elia Stupka, Jason Gardner, Christof von Kalle, Claudio Bordignon, Fabio Ciceri, Attilio Rovelli, Maria Grazia Roncarolo, Alessandro Aiuti, Maria Sessa, and Luigi Naldini Science 23 August 2013: 1233158Published online 11 July 2013 [DOI:10.1126/science.1233158]
February 5 - Shannon Rego, BS, MA
Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution
Reference(s): Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution Andrew B. Stergachis, Eric Haugen, Anthony Shafer, Wenqing Fu, Benjamin Vernot, Alex Reynolds, Anthony Raubitschek, Steven Ziegler, Emily M. LeProust, Joshua M. Akey, and John A. Stamatoyannopoulos. Science 13 December 2013: 1367-1372. [DOI:10.1126/science.1243490]
January 29 - Andrea Kwan, MS, LCGC
miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models
Reference(s): miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. Cheng PH, Li CL, Chang YF, Tsai SJ, Lai YY, Chan AW, Chen CM, Yang SH. Am J Hum Genet. 2013 Aug 8;93(2):306-12. - PubMed PMID: 23810380
January 22 - Ashley Navarro, BS
A genome-wide association study of breast cancer in women of African ancestry
Reference(s): Chen,F. et al. (2013) A genome-wide association study of breast cancer in women of African ancestry. Hum. Genet., 132, 39–48.
January 15 - Katelyn Kobara, BS
Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation
Reference(s): Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation. Ulrich Pannicke, Ph.D., Bernd Baumann, Ph.D., Sebastian Fuchs, M.Sc., Philipp Henneke, M.D., Anne Rensing-Ehl, M.D., Marta Rizzi, M.D., Ph.D., Ales Janda, M.D., Ph.D., Katrin Hese, Ph.D., Michael Schlesier, Ph.D., Karlheinz Holzmann, Ph.D., Stephan Borte, M.D., Constanze Laux, Eva-Maria Rump, Alan Rosenberg, M.D., Teresa Zelinski, Ph.D., Hubert Schrezenmeier, M.D., Thomas Wirth, Ph.D., Stephan Ehl, M.D., Marlis L. Schroeder, M.D., and Klaus Schwarz, M.D. N Engl J Med 2013; 369:2504-2514December 26, 2013DOI: 10.1056/NEJMoa1309199
January 8 - Gregory Enns, MB ChB
mTOR: a new pathway for mitochondrial disease therapy
Reference(s): mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, Oh K, Wasko BM, Ramos FJ, Palmiter RD, Rabinovitch PS, Morgan PG, Sedensky MM, Kaeberlein M. Science. 2013 Dec 20;342(6165):1524-8. doi: 10.1126/science.1244360. Epub 2013 Nov 14.
Neurometabolic disease: Treating mitochondrial diseases with mTOR inhibitors-a potential treatment for Leigh syndrome? Geach T. Nat Rev Neurol. 2014 Jan;10(1):2. doi: 10.1038/nrneurol.2013.251. Epub 2013 Dec 3. PMID: 24296657 [PubMed - in process]
December 4 - Jonathan Bernstein, MD, PhD
An unexpected mechanism for congenital asplenia -- a new ribosomopathy
Reference(s): Bolze A, Mahlaoui N, Byun M, Turner B, Trede N, Ellis SR, Abhyankar A, Itan Y, Patin E, Brebner S, Sackstein P, Puel A, Picard C, Abel L, Quintana-Murci L, Faust SN, Williams AP, Baretto R, Duddridge M, Kini U, Pollard AJ, Gaud C, Frange P, Orbach D, Emile JF, Stephan JL, Sorensen R, Plebani A, Hammarstrom L, Conley ME, Selleri L, Casanova JL. Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia. Science. 2013 May 24;340(6135):976-8. doi: 10.1126/science.1234864. Epub 2013 Apr 11. PMID: 23579497
November 20 - Anna-Kaisa Niemi, MD, PhD
"Mitochondrial channelopathy" - periodic paralysis due to mitochondrial defect
Reference(s): Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations. Auré K, Dubourg O, Jardel C, Clarysse L, Sternberg D, Fournier E, Laforêt P, Streichenberger N, Petiot P, Gervais-Bernard H, Vial C, Bedat-Millet AL, Drouin-Garraud V, Bouillaud F, Vandier C, Fontaine B, Lombès A. Neurology. November 19, 2013 81:1810-1818
November 13, 2013 - Kelly Broady, BA
A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection
Reference(s): A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection. Zeron-Medina J, Wang X, Repapi E, Campbell MR, Su D, Castro-Giner F, Davies B, Peterse EF, Sacilotto N, Walker GJ, Terzian T, Tomlinson IP, Box NF, Meinshausen N, De Val S, Bell DA, Bond GL. Cell. 2013 Oct 10;155(2):410-22. - PubMed PMID: 24120139
November 6 - Kimberly Splinter, BA
Topoisomerases facilitate transcription of long genes linked to autism
Reference(s): Topoisomerases facilitate transcription of long genes linked to autism. King IF, Yandava CN, Mabb AM, Hsiao JS, Huang HS, Pearson BL, Calabrese JM, Starmer J, Parker JS, Magnuson T, Chamberlain SJ, Philpot BD, Zylka MJ.
Nature. 2013 Sep 5;501(7465):58-62. - PubMed PMID: 23995680
October 30 - Erica Stricko, BS
A Novel Channelopathy in Pulmonary Arterial Hypertension
Reference(s): A Novel Channelopathy in Pulmonary Arterial Hypertension. Ma, Lijiang, MD, PhD; Roman-Campos, Danilo, PhD; Austin, Eric D, MDView Profile; Eyries, Mélanie, PhD; Sampson, Kevin S, PhD; et al. The New England Journal of Medicine369.4 (Jul 25, 2013): 351-61.
October 16 - Colleen Forsyth Macmurdo, DO
Clinical Whole-Exome Sequencing... 25% isn't bad
Reference(s): Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders. Yaping Yang, Ph.D., et al. October 2, 2013DOI: 10.1056/NEJMoa1306555
October 2 - Anastasia Richardson, BS
Establishing Informed Decision Making or Impeding Autonomy: Published Responses to the 2013 ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing
Reference(s): Green, R. C., Lupinski, J. R., & Biesecker, L. G. (2013). Reporting Genomic Sequencing Results to Ordering Clinicans- Incidental but not Exceptional. JAMA, 310(4), 365-366
Klitzman, R. et al. (2013). Return of Secondary Genomic Findings vs Patient Autonomy Implications for Medical Care. JAMA, 310(4), 369-370
Mcguire, A. L. et al (2013). Ethics and Genomic Incidental Findings. Science Express, Policy Forum. DOI: 10.1126/science.1240156
Ross, L. F. et al. (2013). Mandatory Extended Searches in All Genome Sequencing- “Incidental Findings,” Patient Autonomy, and Shared Decision Making. JAMA, 310(4), 367-368
Wolf, S. et al. (2013). Patient Autonomy and Incidental Findings in Clinical Genomics. Science Express, Policy Forum. DOI: 10.1126/science.1239119
September 25 - Jake Sherkow, JD
The Future of Gene Patents and the Implications for Medicine
Reference(s): The Future of Gene Patents and the Implications for Medicine. Sherkow JS, Greely HT. JAMA Intern Med. 2013 Jul 29 - PubMed PMID: 23896757
May 27 - Susan Schelley, MPH, CGC, LGC
Mutations in NDUFB11 causes MLS syndrome
Reference(s): Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome. van Rahden VA, Fernandez-Vizarra E, Alawi M, Brand K, Fellmann F, Horn D, Zeviani M, Kutsche K. Am J Hum Genet. 2015 Apr 2;96(4):640-50. PMID: 25772934
May 20 - Anna Erickson, DPhil
Clinical significance of 3-methylcrotonyl-CoA carboxylase deficiency: an on-going debate
Reference(s): Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD. Shepard PJ, Barshop BA, Baumgartner MR, Hansen JB, Jepsen K, Smith EN, Frazer KA. Genet Med. 2014 Nov 6 PMID: 25356967
May 13 - Rachel Cox, MS, LCGC
Newborn screening for Krabbe disease: improving on a bad idea
Reference(s): Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease. Turgeon CT, Orsini JJ, Sanders KA, Magera MJ, Langan TJ, Escolar ML, Duffner P, Oglesbee D, Gavrilov D, Tortorelli S, Rinaldo P, Raymond K, Matern D. J Inherit Metab Dis. 2015 Mar 12. PMID: 25762404
May 6 - Andrea Hanson-Kahn, MS, LCGC
RNA editing of OPHN1
Reference(s): Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development. Barresi S, Tomaselli S, Athanasiadis A, Galeano F, Locatelli F, Bertini E, Zanni G, Gallo A. PLoS One. 2014;9(3):e91351. PMID: 24637888
April 29 - Louanne Hudgins, MD
NIPT for the masses?
Reference(s): Cell-free DNA Analysis for Noninvasive Examination of Trisomy. Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, Tomlinson MW, Pereira L, Spitz JL, Hollemon D, Cuckle H, Musci TJ, Wapner RJ. N Engl J Med. 2015 Apr 1. PMID: 25830321
April 22 - Natalia Gomez-Ospina, MD, PhD
Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV
Reference(s): Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH. N Engl J Med. 2014 Mar 6;370(10):901-10. PMID: 24597865
April 15 - Joanne Taylor, MS, CGC, LGC
NIPT for all? Are we the gate keepers or the suppliers?
Reference(s): Current controversies in prenatal diagnosis 1: NIPT for chromosome abnormalities should be offered to women with low a priori risk. Van Lith JM, Faas BH, Bianchi DW. Prenat Diagn. 2015 Jan;35(1):8-14. PMID: 25393690
Obstetricians and gynecologists' practice and opinions of expanded carrier testing and noninvasive prenatal testing. Benn P, Chapman AR, Erickson K, Defrancesco MS, Wilkins-Haug L, Egan JF, Schulkin J. Prenat Diagn. 2014 Feb;34(2):145-52. PMID: 24222397
April 8 - Kelly Ormond, MS, CGC, LGC
Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States
Reference(s): Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. de Graaf G, Buckley F, Skotko BG. Am J Med Genet A. 2015 Apr;167(4):756-67. PMID: 25822844
April 1 - Aaron Wenger, PhD
The human splicing code reveals new insights int the genetic determinants of disease
Reference(s): RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ. Science. 2015 Jan 9;347(6218):1254806. PMID: 25525159
March 4 - Dave A. Stevenson, MD
Congenital contractures due to NALCN
Reference(s): De Novo Mutations in NALCN Cause a Syndrome Characterized by Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay. Chong JX, McMillin MJ, Shively KM, Beck AE, Marvin CT, Armenteros JR, Buckingham KJ, Nkinsi NT, Boyle EA, Berry MN, Bocian M, Foulds N, Uzielli ML, Haldeman-Englert C, Hennekam RC, Kaplan P, Kline AD, Mercer CL, Nowaczyk MJ, Wassink-Ruiter JS, McPherson EW, Moreno RA, Scheuerle AE, Shashi V, Stevens CA, Carey JC, Monteil A, Lory P, Tabor HK, Smith JD, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ. Am J Hum Genet. 2015 Feb 12 - PubMed PMID: 25683120
February 25 - Julia Platt, MS, LCGC
Triheptanoin: A promising therapeutic for GLUT1 deficiency
Reference(s): Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
February 18 - Archana Lal, MD (LKSC 203/204)
Delineating the 15q13.3 microdeletion phenotype
Reference(s): Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature. Lowther C, Costain G, Stavropoulos DJ, Melvin R, Silversides CK, Andrade DM, So J, Faghfoury H, Lionel AC, Marshall CR, Scherer SW, Bassett AS. Genet Med. 2015 Feb;17(2):149-57. - PubMed PMID: 25077648
February 11 - Christian Kunder, MD, PhD
Biallelic Mismatch Repair Deficiency Patients and Their Tumors
Reference(s): Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Shlien A, Campbell BB, de Borja R, Alexandrov LB, Merico D, Wedge D, Van Loo P, Tarpey PS, Coupland P, Behjati S, Pollett A, Lipman T, Heidari A, Deshmukh S, Avitzur N, Meier B, Gerstung M, Hong Y, Merino DM, Ramakrishna M, Remke M, Arnold R, Panigrahi GB, Thakkar NP, Hodel KP, Henninger EE, Göksenin AY, Bakry D, Charames GS, Druker H, Lerner-Ellis J, Mistry M, Dvir R, Grant R, Elhasid R, Farah R, Taylor GP, Nathan PC, Alexander S, Ben-Shachar S, Ling SC, Gallinger S, Constantini S, Dirks P, Huang A, Scherer SW, Grundy RG, Durno C, Aronson M, Gartner A, Meyn MS, Taylor MD, Pursell ZF, Pearson CE, Malkin D, Futreal PA, Stratton MR, Bouffet E, Hawkins C, Campbell PJ, Tabori U; for the Biallelic Mismatch Repair Deficiency Consortium. Nat Genet. 2015 Feb 2 - PubMed PMID: 25642631
February 4 - Sophie Blease, MSc
Next-generation sequencing identifies rare variants associated with Noonan syndrome
Reference(s): Next-generation sequencing identifies rare variants associated with Noonan syndrome. Peng-Chieh Chena, Jiani Yind, Hui-Wen Yuc, Tao Yuanb, Minerva Fernandezd, Christina K. Yunge, Quang M. Trinhe, Vanya D. Peltekovae, Jeffrey G. Reidf, Erica Tworog-Dubeb, Margaret B. Morganf, Donna M. Muznyf, Lincoln Steine, John D. McPhersone, Amy E. Robertsg, Richard A. Gibbsf, Benjamin G. Neeld, and Raju Kucherlapati. (2014) Proc Natl Acad Sci U S A 111:11473–11478.
January 28 - Gregory Enns, MB ChB
NGLY1 deficiency – new insights into the pathogenesis of a novel disorder of the endoplasmic reticulum-associated degradation (ERAD) pathway
Reference(s): Endo-β-N-acetylglucosaminidase forms N-GlcNAc protein aggregates during ER-associated degradation in Ngly1-defective cells. Huang C, Harada Y, Hosomi A, Masahara-Negishi Y, Seino J, Fujihira H, Funakoshi Y, Suzuki T, Dohmae N, Suzuki T. Proc Natl Acad Sci U S A. 2015 Jan 20 - PubMed PMID: 25605922
January 21 - Allie Newhall, BS
New Disorder of Gigantism and Acromegaly: X-linked Acrogigantism
Reference(s): Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. Trivellin G1, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH, Castermans E, Villa C, Dimopoulos A, Chittiboina P, Xekouki P, Shah N, Metzger D, Lysy PA, Ferrante E, Strebkova N, Mazerkina N, Zatelli MC, Lodish M, Horvath A, de Alexandre RB, Manning AD, Levy I, Keil MF, Sierra Mde L, Palmeira L, Coppieters W, Georges M, Naves LA, Jamar M, Bours V, Wu TJ, Choong CS, Bertherat J, Chanson P, Kamenický P, Farrell WE, Barlier A, Quezado M, Bjelobaba I, Stojilkovic SS, Wess J, Costanzi S, Liu P, Lupski JR, Beckers A, Stratakis CA. N Engl J Med. 2014 Dec 18;371(25):2363-74.
January 14 - Jonathan Bernstein, MD, PhD
New genes for an old phenotype - Catel Manzke Syndrome
Reference(s): Homozygous and Compound-Heterozygous Mutations in TGDS Cause Catel-Manzke Syndrome. Ehmke N, Caliebe A, Koenig R, Kant SG, Stark Z, Cormier-Daire V, Wieczorek D, Gillessen-Kaesbach G, Hoff K, Kawalia A, Thiele H, Altmüller J, Fischer-Zirnsak B, Knaus A, Zhu N, Heinrich V, Huber C, Harabula I, Spielmann M, Horn D, Kornak U, Hecht J, Krawitz PM, Nürnberg P, Siebert R, Manzke H, Mundlos S. Am J Hum Genet. 2014 Dec 4;95(6):763-70. - PubMed PMID: 25480037
IMPAD1 mutations in two Catel-Manzke like patients. Nizon M, Alanay Y, Tuysuz B, Kiper PO, Geneviève D, Sillence D, Huber C, Munnich A, Cormier-Daire V. Am J Med Genet A. 2012 Sep;158A(9):2183-7. - PubMed PMID: 22887726
January 7 - Mark Ewalt, MD
Clonal Hematopoiesis in the Elderly
Reference(s): Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landén M, Höglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Grönberg H, Hultman CM, McCarroll SA. N Engl J Med. 2014 Dec 25;371(26):2477-87. - PubMed PMID: 25426838
Age-related clonal hematopoiesis associated with adverse outcomes. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. N Engl J Med. 2014 Dec 25;371(26):2488-98. - PubMed PMID: 25426837
December 3 - Kerry Kingham, MS, CGC
Hereditary Diffuse Gastric Cancer - Gastrectomy or no gastrectomy; that is the question
Reference(s): Germline Mutations in MAP3K6 Are Associated with Familial Gastric Cancer. Gaston D, Hansford S, Oliveira C, Nightingale M, Pinheiro H, Macgillivray C, Kaurah P, Rideout AL, Steele P, Soares G, Huang WY, Whitehouse S, Blowers S, LeBlanc MA, Jiang H, Greer W, Samuels ME, Orr A, Fernandez CV, Majewski J, Ludman M, Dyack S, Penney LS, McMaster CR, Huntsman D, Bedard K. PLoS Genet. 2014 Oct;10(10):e1004669. - PubMed PMID: 25340522
November 26 - NO HGJC
November 19 - Amitha Ananth, MD
Autism and Mental Retardation Among Offspring Born After In Vitro Fertilization
Reference(s): Autism and mental retardation among offspring born after in vitro fertilization. Sandin S, Nygren KG, Iliadou A, Hultman CM, Reichenberg A. JAMA. 2013 Jul 3;310(1):75-84. - PubMed PMID: 23821091
November 12 - Della Bro, BA
Somatic mutations in cerebral cortical malformations
Reference(s): Somatic mutations in cerebral cortical malformations. Jamuar SS, Lam AT, Kircher M, D'Gama AM, Wang J, Barry BJ, Zhang X, Hill RS, Partlow JN, Rozzo A, Servattalab S, Mehta BK, Topcu M, Amrom D, Andermann E, Dan B, Parrini E, Guerrini R, Scheffer IE, Berkovic SF, Leventer RJ, Shen Y, Wu BL, Barkovich AJ, Sahin M, Chang BS, Bamshad M, Nickerson DA, Shendure J, Poduri A, Yu TW, Walsh CA. N Engl J Med. 2014 Aug 21;371(8):733-43. - PubMed PMID: 25140959
November 5 - Elise Calonico, BS
A mutation of COX6A1 causes a recessive axonal or mixed form of CMT
Reference(s): A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.
Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K.
Am J Hum Genet. 2014 Sep 4;95(3):294-300. - PubMed PMID: 25152455
October 29 - RJ Okamura, BS
It's got to be in here somewhere... Analyzing CNV data to discover genes associated with developmental delay
Reference(s): Refining analyses of copy number variation identifies specific genes associated with developmental delay. Coe BP, Witherspoon K, Rosenfeld JA, van Bon BWM, Silfhoute ATV, Bosco P, Friend KL, Baker C, Buono S, Vissers LELM, Schurrs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, Reijnders MRF, Torchia BS, Peeters H, Thompson E, O’Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford H, Haan E, Gecz J, de Vries BBA, Romano C, Eichler EE. Nature Genetics. 2014 Aug 20;46(10):1063-107. – PubMed PMID: 25217958.
October 22 - NO HGJC (ASHG)
October 15 - Ping Gong, BS
Parental Somatic Mosaicism and Implications for Recurrence
Reference(s): Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders.
Campbell IM, Yuan B, Robberecht C, Pfundt R, Szafranski P, McEntagart ME, Nagamani SC, Erez A, Bartnik M, Wiśniowiecka-Kowalnik B, Plunkett KS, Pursley AN, Kang SH, Bi W, Lalani SR, Bacino CA, Vast M, Marks K, Patton M, Olofsson P, Patel A, Veltman JA, Cheung SW, Shaw CA, Vissers LE, Vermeesch JR, Lupski JR, Stankiewicz P.
Am J Hum Genet. 2014 Aug 7;95(2):173-82. - PubMed PMID: 25087610
October 8 - Rebecca Luiten, BS
MO1: A New Mendelian Obesity Syndrome
Reference(s): Morbid obesity resulting from inactivation of the ciliary protein CEP19 in humans and mice.
Shalata A, Ramirez MC, Desnick RJ, Priedigkeit N, Buettner C, Lindtner C, Mahroum M, Abdul-Ghani M, Dong F, Arar N, Camacho-Vanegas O, Zhang R, Camacho SC, Chen Y, Ibdah M, DeFronzo R, Gillespie V, Kelley K, Dynlacht BD, Kim S, Glucksman MJ, Borochowitz ZU, Martignetti JA. Am J Hum Genet. 2013 Dec 5;93(6):1061-71. - PubMed PMID: 24268657
October 1 - Colleen Macmurdo, DO
CHARGE-Like Presentation, Craniosynostosis and Mild Mowat-Wilson Syndrome
Reference(s): Wenger TL et al. CHARGE-like presentation, craniosyntosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. Am J Med Genet A. 2014 Oct;164(10):2557-66. PMID: 25123255
September 24 - Melanie Manning, MD
FORGE-ing Ahead with Gene Discovery
Reference(s): Beaulieu CL et al., FORGE Canada Consortium: Outcomes of a 2-year national rare-disease gene-discovery project. AJHG 94:809-817, 2014. PMID: 24906018