Dataset Information

Characterization of autosomal copy-number variation in African Americans: the HyperGEN Study.

ABSTRACT: African Americans are a genetically diverse population with a high burden of many, common heritable diseases. However, our understanding of genetic variation in African Americans is substandard because of a lack of published population-based genetic studies. We report the distribution of copy-number variation (CNV) in African Americans collected as part of the Hypertension Genetic Epidemiology Network (HyperGEN) using the Affymetrix 6.0 array and the CNV calling algorithms Birdsuite and PennCNV. We present population estimates of CNV from 446 unrelated African-American subjects randomly selected from the 451 families collected within HyperGEN. Although the majority of CNVs discovered were individually rare, we found the frequency of CNVs to be collectively high. We identified a total of 11?070 CNVs greater than 10?kb passing quality control criteria that were called by both algorithms - leading to an average of 24.8 CNVs per person covering 2214?kb (median). We identified 1541 unique copy-number variable regions, 309 of which did not overlap with the Database of Genomic Variants. These results provide further insight into the distribution of CNV in African Americans.

SUBMITTER: Wineinger NE

PROVIDER: S-EPMC3230358 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Characterization of autosomal copy-number variation in African Americans: the HyperGEN Study.

Wineinger Nathan E NE Pajewski Nicholas M NM Kennedy Richard E RE Wojczynski Mary K MK Vaughan Laura K LK Hunt Steven C SC Gu C Charles CC Rao Dabeeru C DC Lorier Rachel R Broeckel Ulrich U Arnett Donna K DK Tiwari Hemant K HK

European journal of human genetics : EJHG 20110615 12

African Americans are a genetically diverse population with a high burden of many, common heritable diseases. However, our understanding of genetic variation in African Americans is substandard because of a lack of published population-based genetic studies. We report the distribution of copy-number variation (CNV) in African Americans collected as part of the Hypertension Genetic Epidemiology Network (HyperGEN) using the Affymetrix 6.0 array and the CNV calling algorithms Birdsuite and PennCNV. ...[more]

PMID: 21673747

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Project description:Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR?=?2.59; p?=?0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR?=?5.62; p?=?0.0002), but not in females (OR?=?1.19, p?=?0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR?=?2.59; p?=?0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.

Dataset Information

Characterization of autosomal copy-number variation in African Americans: the HyperGEN Study.

Publications

Characterization of autosomal copy-number variation in African Americans: the HyperGEN Study.

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