The chromosomes we inherit from our parents are not exact copies but mosaics of their chromosomes. These mosaics are created during the formation of eggs and sperm when cells cut chromosomes up and re-attach them, sometimes in new combinations (recombination). We discovered that our cells make an unexpectedly large number of errors in this process leading to changes in DNA (mutations).
We are interested in the mechanisms underlying recombination and mutagenesis. We perform a range of whole-genome experimental assays and leverage large-scale human genetic datasets using statistical analyses and machine learning.
Quick links
(Science 2023) Meiotic DNA breaks lead to de novo mutations in humans through repair with a repertoire of error-prone mechanisms.
(Science 2019) Factors influencing meiotic recombination revealed by statistical analyses of whole-genome DNA sequencing of single sperm cells.
Our goal is to understand processes that impact DNA in the germline and how they affect human health and diversity. Many of these processes are complex and dynamic, involving the interplay of numerous proteins.
Our approach is data driven. We perform a range of experimental assays, including CRISPR-Cas9 mediated genome-editing, to learn how these proteins interact with the genome. We also utilise large-scale genetic and phenotypic datasets in humans (e.g., the UK Biobank) to understand their impacts on our health.
We weave together these diverse datasets for mechanistic inference using statistical analyses and machine learning.
2023
Meiotic DNA breaks drive multifaceted mutagenesis in the human gemline.
Hinch, R., Donnelly, P., Hinch, A.G.
Science – 382(6674):eadh2531.
2023
Characterisation of meiotic recombination intermediates through gene knockouts in founder hybrid mice.
Davies, B., Zhang, G., Moralli, D., Alghadban, S., Biggs, D., Preece, C., Donnelly, P.,Hinch, A.G.
Genome Res, – 33(11):2018-2027.
2020
The configuration of RPA, RAD51 and DMC1 binding in meiosis reveals the nature of critical recombination intermediates.
Hinch, A.G.*, Becker, P. W., Li, T., Moralli, D., Zhang, G., et al.
Molecular Cell – 79(4):689-701.e10.
2019
Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm.
Hinch, A.G., Zhang, G., Becker, P.W., Moralli, D., Hinch, R., et al.
Science – 363(6433):eaau8861.
2011
The landscape of recombination in African Americans.
Hinch, A.G., Tandon, A., Patterson, N., Song, Y., Rohland, N. et al.
Nature – 476(7359):170-5.
2016
Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice.
Davies ,B. , Hatton, E., Altemose, N., Hussin, J.G., Pratto, F., Zhang, G., Hinch, A.G., et al.
Nature – 530(7589):171-176.
2020
Molecular structures and mechanisms of DNA break processing in mouse meiosis.
Yamada, S., Hinch, A. G. , Kamido, H., Zhang, Y., Edelmann, W., Keeney, S.
Genes Dev. – 4(11-12):806-818.