Research Guides: Genetics Journal Club: 2020-21

February 2021

A Population-Based Study of Genes Previously Implicated in Breast Cancer
Hu C, Hart SN, Gnanaolivu R, et al. A Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936
Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women
Breast Cancer Association Consortium, Dorling L, Carvalho S, et al. Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021;384(5):428-439. doi:10.1056/NEJMoa1913948
Which Genes for Hereditary Breast Cancer?
Narod, S.A. (2021). Which genes for hereditary breast cancer? N Engl J Med 2021; 384:471-473
DOI: 10.1056/NEJMe2035083
Ochronosis
Di Matteo B, Marcacci M. Ochronosis. N Engl J Med. 2021;384(5):461. doi:10.1056/NEJMicm2025932
Race and Genetic Ancestry in Medicine — A Time for Reckoning with Racism
Borrell LN, Elhawary JR, Fuentes-Afflick E, et al. Race and Genetic Ancestry in Medicine - A Time for Reckoning with Racism. N Engl J Med. 2021;384(5):474-480. doi:10.1056/NEJMms2029562

January 2021

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med. 2021;384(3):252-260. doi:10.1056/NEJMoa2031054
Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type
Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type. N Engl J Med. 2021 Jan 14;384(2):185-187. doi: 10.1056/NEJMc2030638. PMID: 33497555.
Human Molecular Genetics and Genomics-Important Advances and Exciting Possibilities
Collins, F. S., Doudna, J. A., Lander, E. S., & Rotimi, C. N. (2021). Human Molecular Genetics and Genomics-Important Advances and Exciting Possibilities. The New England journal of medicine.
Induction of Fetal Hemoglobin by Gene Therapy
Walters MC. Induction of Fetal Hemoglobin by Gene Therapy. N Engl J Med. 2021;384(3):284-285. doi:10.1056/NEJMe2034338
Misrepresenting Race — The Role of Medical Schools in Propagating Physician Bias
Amutah C, Greenidge K, Mante A, et al. Misrepresenting Race - The Role of Medical Schools in Propagating Physician Bias [published online ahead of print, 2021 Jan 6]. N Engl J Med. 2021;10.1056/NEJMms2025768. doi:10.1056/NEJMms2025768
Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease
Esrick EB, Lehmann LE, Biffi A, et al. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. N Engl J Med. 2021;384(3):205-215. doi:10.1056/NEJMoa2029392

December 2020

Cardiac Macrophages — Keeping the Engine Running Clean
McNally EM. Cardiac Macrophages - Keeping the Engine Running Clean. N Engl J Med. 2020;383(25):2474-2476. doi:10.1056/NEJMcibr2030271
Hiding in Plain Sight — Somatic Mutation in Human Disease
Levy-Lahad E, King MC. Hiding in Plain Sight - Somatic Mutation in Human Disease. N Engl J Med. 2020;383(27):2680-2682. doi:10.1056/NEJMe2030754
Prostate Cancer Progression and the Epigenome
Arap W, Pasqualini R, Costello JF. Prostate Cancer Progression and the Epigenome. N Engl J Med. 2020;383(23):2287-2290. doi:10.1056/NEJMcibr2030475
Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease
Beck DB, Ferrada MA, Sikora KA, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020;383(27):2628-2638. doi:10.1056/NEJMoa2026834

November 2020

Banning Genetic Discrimination in Life Insurance — Time to Follow Florida’s Lead
Rothstein, M. A., & Brothers, K. B. (2020). Banning Genetic Discrimination in Life Insurance—Time to Follow Florida’s Lead. New England Journal of Medicine, 383(22), 2099-2101.
Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis
Sparks TN, Lianoglou BR, Adami RR, et al. Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. N Engl J Med. 2020;383(18):1746-1756. doi:10.1056/NEJMoa2023643
Killing the Pathogen and Sparing the Placenta
Mysorekar IU. Killing the Pathogen and Sparing the Placenta. N Engl J Med. 2020;383(21):2080-2082. doi:10.1056/NEJMcibr2028357
Lineage-Independent Tumors in Bilateral Neuroblastoma
Coorens THH, Farndon SJ, Mitchell TJ, et al. Lineage-Independent Tumors in Bilateral Neuroblastoma. N Engl J Med. 2020;383(19):1860-1865. doi:10.1056/NEJMoa2000962

October 2020

Fibroblasts in Rheumatoid Arthritis
Chu CQ. Fibroblasts in Rheumatoid Arthritis. N Engl J Med. 2020;383(17):1679-1681. doi:10.1056/NEJMcibr2024718
Genomewide Association Study of Severe Covid-19 with Respiratory Failure
Severe Covid-19 GWAS Group, Ellinghaus D, Degenhardt F, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020;383(16):1522-1534. doi:10.1056/NEJMoa2020283
Nonimmune Hydrops Fetalis — More Than Meets the Eye?
Kilby MD. Nonimmune Hydrops Fetalis - More Than Meets the Eye?. N Engl J Med. 2020;383(18):1785-1786. doi:10.1056/NEJMe2029914

September 2020

Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema
Cohn DM, Viney NJ, Fijen LM, Schneider E, Alexander VJ, Xia S, Kaeser GE, Nanavati C, Baker BF, Geary RS, Levi M, Meijers JCM, Stroes ESG. Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema. N Engl J Med. 2020 Sep 24;383(13):1242-1247. doi: 10.1056/NEJMoa1915035. Epub 2020 Sep 2. PMID: 32877578.
Causal Genetic Variants in Stillbirth
Stanley KE, Giordano J, Thorsten V, Buchovecky C, Thomas A, Ganapathi M, Liao J, Dharmadhikari AV, Revah-Politi A, Ernst M, Lippa N, Holmes H, Povysil G, Hostyk J, Parker CB, Goldenberg R, Saade GR, Dudley DJ, Pinar H, Hogue C, Reddy UM, Silver RM, Aggarwal V, Allen AS, Wapner RJ, Goldstein DB. Causal Genetic Variants in Stillbirth. N Engl J Med. 2020 Sep 17;383(12):1107-1116. doi: 10.1056/NEJMoa1908753. Epub 2020 Aug 12. PMID: 32786180; PMCID: PMC7604888.
Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Merke DP, Auchus RJ. Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. N Engl J Med. 2020 Sep 24;383(13):1248-1261. doi: 10.1056/NEJMra1909786. PMID: 32966723.
Genomic Insights into Stillbirth
Wojcik MH. Genomic Insights into Stillbirth. N Engl J Med. 2020 Sep 17;383(12):1182-1183. doi: 10.1056/NEJMe2016410. Epub 2020 Aug 12. PMID: 32786182.
Humoral Immune Response to SARS-CoV-2 in Iceland
Gudbjartsson DF, Norddahl GL, Melsted P, et al. Humoral Immune Response to SARS-CoV-2 in Iceland. N Engl J Med. 2020 Oct 29;383(18):1724-1734. doi: 10.1056/NEJMoa2026116. Epub 2020 Sep 1. PMID: 32871063; PMCID: PMC7494247.
Janus Kinase Inhibition in the Aicardi–Goutières Syndrome
Vanderver A, Adang L, Gavazzi F, McDonald K, Helman G, Frank DB, Jaffe N, Yum SW, Collins A, Keller SR, Lebon P, Meritet JF, Rhee J, Takanohashi A, Armangue T, Ulrick N, Sherbini O, Koh J, Peer K, Besnier C, Scher C, Boyle K, Dubbs H, Kramer-Golinkoff J, Pizzino A, Woidill S, Shults J. Janus Kinase Inhibition in the Aicardi-Goutières Syndrome. N Engl J Med. 2020 Sep 3;383(10):986-989. doi: 10.1056/NEJMc2001362. PMID: 32877590; PMCID: PMC7495410.
Trained Innate Immunity, Epigenetics, and Covid-19
Mantovani A, Netea MG. Trained Innate Immunity, Epigenetics, and Covid-19. N Engl J Med. 2020 Sep 10;383(11):1078-1080. doi: 10.1056/NEJMcibr2011679. PMID: 32905684.

August 2020

Causal Genetic Variants in Stillbirth
Stanley KE, Giordano J, Thorsten V, et al. Causal Genetic Variants in Stillbirth [published online ahead of print, 2020 Aug 12]. N Engl J Med. 2020;10.1056/NEJMoa1908753. doi:10.1056/NEJMoa1908753
Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells
Walker MA, Lareau CA, Ludwig LS, et al. Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells [published online ahead of print, 2020 Aug 12]. N Engl J Med. 2020;10.1056/NEJMoa2001265. doi:10.1056/NEJMoa2001265
Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations
Baudou E, Lespine A, Durrieu G, et al. Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations. N Engl J Med. 2020;383(8):787-789. doi:10.1056/NEJMc1917344
Genomic Insights into Stillbirth
Wojcik MH. Genomic Insights into Stillbirth [published online ahead of print, 2020 Aug 12]. N Engl J Med. 2020;10.1056/NEJMe2016410. doi:10.1056/NEJMe2016410
When E-Cadherin Becomes Unstuck in Cancer
O'Driscoll L. When E-Cadherin Becomes Unstuck in Cancer. N Engl J Med. 2020;383(9):871-873. doi:10.1056/NEJMcibr2018713

July 2020

Etiologic Index — A Case-Only Measure of BRCA1/2–Associated Cancer Risk
Hughley, R., Karlic, R., Joshi, H., Turnbull, C., Foulkes, W. D., & Polak, P. (2020). Etiologic Index—A Case-Only Measure of BRCA1/2–Associated Cancer Risk. New England Journal of Medicine, 383(3), 286-288.
Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population
Martin, C. L., Wain, K. E., Oetjens, M. T., Tolwinski, K., Palen, E., Hare-Harris, A., ... & Myers, S. M. (2020). Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population. JAMA psychiatry.
Presence of Genetic Variants Among Young Men With Severe COVID-19
van der Made, C. I., Simons, A., Schuurs-Hoeijmakers, J., van den Heuvel, G., Mantere, T., Kersten, S., ... & Hofste, T. (2020). Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA.
Zika Virus Disease and Pregnancy Outcomes in Colombia
Ospina, M. L., Tong, V. T., Gonzalez, M., Valencia, D., Mercado, M., Gilboa, S. M., ... & Pardo, L. (2020). Zika Virus Disease and Pregnancy Outcomes in Colombia. New England Journal of Medicine, 383(6), 537-545.
RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares
Orange, D. E., Yao, V., Sawicka, K., Fak, J., Frank, M. O., Parveen, S., ... & Troyanskaya, O. G. (2020). RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares. New England Journal of Medicine, 383(3), 218-228.

June 2020

Detection of Structural Rearrangements in Embryos
Madjunkova S, Sundaravadanam Y, Antes R, et al. Detection of Structural Rearrangements in Embryos. N Engl J Med. 2020;382(25):2472-2474. doi:10.1056/NEJMc1913370
Givosiran — Running RNA Interference to Fight Porphyria Attacks
Gonzalez-Aseguinolaza G. Givosiran - Running RNA Interference to Fight Porphyria Attacks. N Engl J Med. 2020;382(24):2366-2367. doi:10.1056/NEJMe2010986
How to Discover Antiviral Drugs Quickly
Parks JM, Smith JC. How to Discover Antiviral Drugs Quickly. N Engl J Med. 2020;382(23):2261-2264. doi:10.1056/NEJMcibr2007042
Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa
John CC, Opoka RO, Latham TS, et al. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020;382(26):2524-2533. doi:10.1056/NEJMoa2000146
Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria
Balwani M, Sardh E, Ventura P, et al. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020;382(24):2289-2301. doi:10.1056/NEJMoa1913147
Stargardt Juvenile Macular Degeneration
Oh JK, Tsang SH. Stargardt Juvenile Macular Degeneration. N Engl J Med. 2020;382(24):2353. doi:10.1056/NEJMicm1913388
WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition
Lee YR, Yehia L, Kishikawa T, et al. WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition. N Engl J Med. 2020;382(22):2103-2116. doi:10.1056/NEJMoa1914919

Hydroxyurea Dose Escalation for Sickle Cell Anemia

In sub-Saharan Africa and India, the numbers of newborns with sickle cell anemia are projected to increase by 30% by 2050. Without newborn screening programs and appropriate care, an estimated 50 to 90% of these children will die before 5 years of age. New research findings are summarized in a short video.

Genetics Journal Club: 2020-21

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