Excess of runs of homozygosity is associated with severe cognitive impairment in intellectual disability

Genetics in Medicine

Volumn 17, Issue 5, 2015, Pages 396-399

  Gandin, Ilaria ^a   Faletra, Flavio ^b   Faletra, Francesca ^b   Carella, Massimo ^c   Pecile, Vanna ^b   Ferrero, Giovanni B ^d   Biamino, Elisa ^d   Palumbo, Pietro ^c   Palumbo, Orazio ^c   Bosco, Paolo ^e   Romano, Corrado ^e   Belcaro, Chiara ^a   Vozzi, Diego ^b   D'Adamo, Adamo P ^a,b  

^a UNIVERSITY OF TRIESTE   (Italy)

^b INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

^c CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

^d UNIVERSITY OF TURIN   (Italy)

^e OASI RESEARCH INSTITUTE IRCCS   (Italy)

Author keywords

Inbreeding; intellectual disability; runs of homozygosity

Indexed keywords

ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE SEVERITY; DNA STRUCTURE; FEMALE; GENETIC ASSOCIATION; GENETIC RISK; HOMOZYGOSITY; HUMAN; HUMAN GENOME; INTELLECTUAL IMPAIRMENT; INTELLIGENCE QUOTIENT; MAJOR CLINICAL STUDY; MALE; RUNS OF HOMOZYGOSITY; COGNITION DISORDERS; CONSANGUINITY; GENETIC ASSOCIATION STUDY; GENETICS; HOMOZYGOTE; INTELLECTUAL DISABILITY; MUTATION; ODDS RATIO; PHENOTYPE; RECESSIVE GENE;

COGNITION DISORDERS; CONSANGUINITY; FEMALE; GENES, RECESSIVE; GENETIC ASSOCIATION STUDIES; HOMOZYGOTE; HUMANS; INTELLECTUAL DISABILITY; MALE; MUTATION; ODDS RATIO; PHENOTYPE;

EID: 84928888838     PISSN: 10983600     EISSN: 15300366     Source Type: Journal    
DOI: 10.1038/gim.2014.118     Document Type: Article

References (18)

1. Leonard H, Wen X. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment Retard Dev Disabil Res Rev 2002;8:117-134.
2. Hochstenbach R, Buizer-Voskamp JE, Vorstman JA, Ophoff RA. Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. Cytogenet Genome Res 2011;135:174-202.
3. Rauch A, Hoyer J, Guth S, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A 2006;140:2063-2074.
4. Vissers LE, de Ligt J, Gilissen C, et al. A de novo paradigm for mental retardation. Nat Genet 2010;42:1109-1112.
5. de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 2012;367:1921-1929.
6. Abou Jamra R, Wohlfart S, Zweier M, et al. Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity. Eur J Hum Genet 2011;19:1161-1166.
7. Cąlkan M, Chong JX, Uricchio L, et al. Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. Hum Mol Genet 2011;20:1285-1289.
8. Najmabadi H, Hu H, Garshasbi M, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 2011;478:57-63.
9. McQuillan R, Eklund N, Pirastu N, et al.; ROHgen Consortium. Evidence of inbreeding depression on human height. PLoS Genet 2012;8:e1002655.
10. Simón-Sánchez J, Kilarski LL, Nalls MA, et al.; International Parkinson's Disease Genomics Consortium; Wellcome Trust Case Control Consortium. Cooperative genome-wide analysis shows increased homozygosity in early onset Parkinson's disease. PLoS One 2012;7:e28787.
11. Ghani M, Sato C, Lee JH, et al. Evidence of recessive Alzheimer disease loci in a Caribbean Hispanic data set: genome-wide survey of runs of homozygosity. JAMA Neurol 2013;70:1261-1267.
12. Keller MC, Simonson MA, Ripke S, et al.; Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS Genet 2012;8:e1002656.
13. Lin PI, Kuo PH, Chen CH, et al. Runs of homozygosity associated with speech delay in autism in a Taiwanese Han population: evidence for the recessive model. PLoS One 2013;8:e72056.
14. Gamsiz ED, Viscidi EW, Frederick AM, et alSimons Simplex Collection Genetics Consortium. Intellectual disability is associated with increased runs of homozygosity in simplex autism. Am J Hum Genet 2013;93:103-109.
15. Kirin M, McQuillan R, Franklin CS, Campbell H, McKeigue PM, Wilson JF. Genomic runs of homozygosity record population history and consanguinity. PLoS One 2010;5:e13996.
16. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559-575.
17. Wang K, Li M, Hadley D, et al. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res 2007;17:1665-1674.
18. Szpiech ZA, Xu J, Pemberton TJ, et al. Long runs of homozygosity are enriched for deleterious variation. Am J Hum Genet 2013;93:90-102.