Autozygosity pilot Born in Bradford

The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.EGA study EGAS00001000462

表亲婚配的后代其基因组中约6%为同源纯合（autozygous）区域，即由血统导致的纯合一致（homozygous identical by descent）；若其祖先存在进一步的近亲血缘，该比例甚至更高。英国存在多个表亲婚配率高达20%-50%的大型族群。对这类个体的样本进行外显子组（exome）测序，既可助力这些族群的遗传健康项目开展，也能为罕见功能丧失突变的相关遗传研究提供数据支撑。本试点研究依托布拉德福德出生队列（Born In Bradford）已有的队列样本开展，将识别出几乎所有等位基因频率低至约1%的变异对应的纯合个体，以及携带数百种全新纯合罕见功能丧失变异的个体；同时将为当前正在设计的更大规模研究的社区关系构建与伦理规范制定提供支持。存储于欧洲基因组-表型组数据库（EGA，European Genome-phenome Archive）中的数据为上述样本的低覆盖度全外显子组测序数据，对应的EGA研究编号为EGAS00001000462