TABLE 2.

A list of interesting, landmark and important articles in the history of medical genetics. Learning questions will be hosted on Children’s National Genetics Education Site (see Table 1)

KEY GENETIC CONCEPTS
Sex chromosome aneuploidy	Ford CE, Jones KW, Polani PE, et al. A sex‐chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet. 1959; 1(7075):711‐3.
Imprinting	Nicholls RD, Knoll JH, Butler MG, et al. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader‐Willi syndrome. Nature. 1989; 342 (6247):281–285.
Genetic Dominance	Wilkie AO. The molecular basis of genetic dominance. J Med Genet. 1994; 31 (2):89–98. Goldstein JL, Brown MS. Familial hypercholesterolemia: identification of a defect in the regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc Natl Acad Sci U S A. 1973 Oct; 70(10):2804‐8.
X‐linked Dominant	Amir, R., Van den Veyver, I., Wan, M. et al. Rett syndrome is caused by mutations in X‐linked MECP2, encoding methyl‐CpG‐binding protein 2. Nat Genet 1999; 23, 185–188.
X‐inactivation	Lyon MF. X‐chromosome inactivation: a repeat hypothesis. Cytogenet Cell Genet. 1998; 80(1‐4):133–137.
The two‐hit phenomenon	Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971; 68(4):820–823.
Gene Dosage	Patel, P., Roa, B., Welcher, A. et al. The gene for the peripheral myelin protein PMP–22 is a candidate for Charcot–Marie–Tooth disease type 1A. Nat Genet 1992; 1, 159–165. P.F. Chance, M.K. Alderson, K.A. Leppig, et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell, 1993; 72:143‐151.
Trinucleotide repeats	Budworth H, McMurray CT. A brief history of triplet repeat diseases. Methods Mol Biol. 2013; 1010:3–17. MacDonald et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72, 971–983.
Mapping a gene to a chromosome	Gusella, J. F., et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 1983; 306, 234–238. King MC. "The race" to clone BRCA1. Science. 2014; 343(6178):1462‐5.
Mosaicism	Lindhurst MJ, Sapp JC, Teer JK et al. A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome. N Engl J Med 2011; 365:611‐619.
Sickle cell disease	Pauling L, Itano HA, Singer SJ, Wells IC. Sickle Cell Anemia, A Molecular Disease. Science 1949; 110(2865): 543‐548. A. C. Allison. Protection afforded by sickle‐cell trait against subtertian malaria infection, Br. Med. J. 1954; 1, 290–294.
CONCEPTS OF TRIPLET REPEAT DISORDERS
Anticipation	P S Harper, H G Harley, W Reardon, and D J Shaw. Anticipation in myotonic dystrophy: new light on an old problem. Am J Hum Genet. 1992 Jul; 51(1): 10–16.
Number of repeats influence expression	Kuhl PA, Pizzuti A, Pieretti M et al. Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell. 1991; 67; 6: 1047‐1058.
PRENATAL GENETICS
Teratology	Jones KL, Smith DW, Ulleland CN, Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet. 1973 Jun 9; 1(7815):1267‐71.
Prevention of Neural Tube Defects	Smithells RW, Sheppard S, Schorah CJ, et al. Apparent prevention of neural tube defects by periconceptional vitamin supplementation. Arch Dis Child. 1981; 56(12):911–918.
Paternal age	Orioli IM, Castilla EE, Scarano G, Mastroiacovo P. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. Am J Med Genet. 1995; 59:209–17.
Circulating cell‐free DNA	Lo YM, Corbetta N, Chamberlain PF, Rai V, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997; 350(9076):485‐7.
Concept of gonadal mosaicism	Pyott, S., Pepin, M., Schwarze, U. et al. Recurrence of perinatal lethal osteogenesis imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance. Genet Med 2011; 13, 125–130.
Twinning	Souter VL, Kapur RP, Nyholt DR, et al. A Report of Dizygous Monochorionic Twins. N Engl J Med 2003; 349:154‐158.
IN THE ERA OF GENOMIC ASSESSMENT & NEXT GENERATION SEQUENCING:
Genome‐wide association studies	Visscher PM, Wray NR, Zhang Q, et al. 10 Years of GWAS Discovery: Biology, Function, and Translation. Am J Hum Genet. 2017; 101(1):5–22.
Chromosomal microarray	Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first‐tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010; 86(5):749‐64.
The role of exome sequencing in molecular discovery	Bamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011; 12(11):745‐55.
Assessing a genetically & phenotypically heterogenous condition	Shen Y, Dies KA, Holm IA, et al. Clinical Genetic Testing for Patients With Autism Spectrum Disorders. Pediatrics 2010, 125 (4) e727‐e735.
Understanding how molecular variants are interpreted in a molecular laboratory	Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17(5):405–424.
Exome sequencing as a first‐tier test for infants with complex disease suggestive of an underlying genetic etiology	Stark, Z., Tan, T., Chong, B. et al. A prospective evaluation of whole‐exome sequencing as a first‐tier molecular test in infants with suspected monogenic disorders. Genet Med 2016; 18, 1090–1096.
The power of segregation analysis	Jarvik GP, Browning BL. Consideration of Cosegregation in the Pathogenicity Classification of Genomic Variants. Am J Hum Genet. 2016; 98(6):1077–1081.
ETHICAL CONCEPTS
Terminology & treatment needs to evolve with patient needs	Lee PA, Houk CP, Ahmed SF, et al. Consensus Statement on Management of Intersex Disorders. Pediatrics Aug 2006, 118 (2) e488‐e500.
History of Gene Patents	Kenneth Offit, Angela Bradbury, Courtney Storm, et al. Gene Patents and Personalized Cancer Care: Impact of the Myriad Case on Clinical Oncology. Journal of Clinical Oncology 2013; 31:21:2743‐2748.
In consideration of population based genetic testing	King M, Levy‐Lahad E, Lahad A. Population‐Based Screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014; 312(11):1091–1092.
Reinterpreting genetic information	Appelbaum PS, Parens E, Berger SM, et al. Is there a duty to reinterpret genetic data? The ethical dimensions. Genet Med. 2020 Mar; 22(3):633‐639.
TREATMENT
Gene Therapy	Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008; 358(21):2240‐8. Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus Sham Control in Infantile‐Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2; 377(18):1723‐1732.
Mutation‐specific treatment	Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011; 365(18):1663‐72.
CRISPR/Cas9	Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual‐RNA‐guided DNA endonuclease in adaptive bacterial immunity. Science. 2012; 337(6096):816–821.
Single‐cell sequencing	Yin Y, Jiang Y, Lam KWG et al. High‐Throughput Single‐Cell Sequencing with Linear Amplification. Molecular Cell. 2019; 76(4):676‐690.