Search tips
Search criteria

Results 1-3 (3)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
author:("Akbar, humera")
PMCID: PMC3305575  PMID: 22353194
2.  Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders 
Human Molecular Genetics  2011;20(17):3366-3375.
Autism spectrum disorders (ASDs) are a heterogeneous group of neuro-developmental disorders. While significant progress has been made in the identification of genes and copy number variants associated with syndromic autism, little is known to date about the etiology of idiopathic non-syndromic autism. Sanger sequencing of 21 known autism susceptibility genes in 339 individuals with high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of 339 probands (1.8%). Additionally, multiple events of oligogenic heterozygosity were seen, affecting 23 of 339 probands (6.8%). Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1, TSC2 and UBE3A by the same sequencing technology revealed that controls were carriers of oligogenic heterozygous events at significantly (P < 0.01) lower rate, suggesting oligogenic heterozygosity as a new potential mechanism in the pathogenesis of ASDs.
PMCID: PMC3153303  PMID: 21624971
3.  Deep resequencing reveals excess rare recent variants consistent with explosive population growth 
Nature Communications  2010;1:131-.
Accurately determining the distribution of rare variants is an important goal of human genetics, but resequencing of a sample large enough for this purpose has been unfeasible until now. Here, we applied Sanger sequencing of genomic PCR amplicons to resequence the diabetes-associated genes KCNJ11 and HHEX in 13,715 people (10,422 European Americans and 3,293 African Americans) and validated amplicons potentially harbouring rare variants using 454 pyrosequencing. We observed far more variation (expected variant-site count ∼578) than would have been predicted on the basis of earlier surveys, which could only capture the distribution of common variants. By comparison with earlier estimates based on common variants, our model shows a clear genetic signal of accelerating population growth, suggesting that humanity harbours a myriad of rare, deleterious variants, and that disease risk and the burden of disease in contemporary populations may be heavily influenced by the distribution of rare variants.
To fully catalogue rare genetic variation in humans, many samples need to be examined. In this study, Coventry et al. resequenced two genes, KCNJ11 and HHEX, in 13,715 humans, and concluded that most of the sequence variation arose recently and that variation is greater than expected.
PMCID: PMC3060603  PMID: 21119644

Results 1-3 (3)