Autozygosity_pilot___Pakistani_from_Birmingham

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 50-80%. 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 British-Pakistani cohort samples from Birmingham 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.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001001025	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 50-80%. 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 British-Pakistani cohort samples from Birmingham 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.	Illumina HiSeq 2000	1156

Publications	Citations
Health and population effects of rare gene knockouts in adult humans with related parents. Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Karczewski KJ, Barnes MR, Barnett AH, Bates C, Bellary S, Bockett NA, Giorda K, Griffiths CJ, Hemingway H, Jia Z, Kelly MA, Khawaja HA, Lek M, McCarthy S, McEachan R, O'Donnell-Luria A, Paigen K, Parisinos CA, Sheridan E, Southgate L, Tee L, Thomas M, Xue Y, Schnall-Levin M, Petkov PM, Tyler-Smith C, Maher ER, Trembath RC, MacArthur DG, Wright J, Durbin R, van Heel DA. Science 352: 2016 474-477	175
Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes. Narasimhan VM, Rahbari R, Scally A, Wuster A, Mason D, Xue Y, Wright J, Trembath RC, Maher ER, van Heel DA, Auton A, Hurles ME, Tyler-Smith C, Durbin R. Nat Commun 8: 2017 303	47
Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria. McGregor TL, Hunt KA, Yee E, Mason D, Nioi P, Ticau S, Pelosi M, Loken PR, Finer S, Lawlor DA, Fauman EB, Huang QQ, Griffiths CJ, MacArthur DG, Trembath RC, Oglesbee D, Lieske JC, Erbe DV, Wright J, van Heel DA. Elife 9: 2020 e54363	33