Matthew Hurles, Ph.D.

Head of Human Genetics and Senior Group Leader, Wellcome Trust Sanger Institute

SFARI Investigator Website

Matthew Hurles is head of human genetics at the Wellcome Sanger Institute and honorary professor of human genetics and genomics at the University of Cambridge. His research has provided new insights into the contributions of genetic variation to rare and common diseases and the factors influencing de novo mutation rates. His research has focused on the genetic causes of severe neurodevelopmental conditions and congenital heart defects.

Hurles leads the Deciphering Developmental Disorders (DDD) study, a UK-wide initiative working with families with genetically undiagnosed developmental conditions. Clinicians in the 24 National Health Service (NHS) Regional Genetics Service clinics throughout the UK and Republic of Ireland recruited participants into the study. Whole-exome sequencing has been conducted in more than 13,000 families (approximately 33,000 individuals in total, including parents).

Hurles’ research has contributed to the identification of more than 50 novel genes involved in developmental conditions (including autism), providing genetic diagnosis for many participants in the DDD study and beyond. His research has also demonstrated a role for de novo variants in regulatory regions in developmental conditions. His team have also developed a website (DECIPHER) that allows for the sharing of information on individuals with rare disorders, accelerating gene discovery.

Hurles also leads the Prenatal Assessment of Genomes and Exomes (PAGE) study, which conducts whole-exome and genome sequencing of fetuses with developmental abnormalities apparent through fetal ultrasound or fetal pathology across the UK. The new insights gained by this study are being used to improve diagnostic methods, allowing better genetics-derived prognoses and more informed parental counselling as well as future management of pregnancy and childbirth.

Hurles also leads the analysis of neurodevelopmental disorders within the 100,000 genomes project. This project involves the whole-genome sequencing of thousands of UK families who are being cared for by the NHS. Hurles also advises the UK BioBank on its whole-genome sequencing initiative, which will contribute to the investigation of the role of rare variants in autism and autistic traits.

SFARI Funded Publications

Genetic correlates of phenotypic heterogeneity in autism. Warrier V., Zhang X., Reed P., Havdahl A., Moore T.M., Cliquet F., Leblond C.S., Rolland T., Rosengren A., EU-AIMS-LEAP, iPSYCH-Autism Working Group, Spectrum 10K and APEX Consortia, Rowitch D., Hurles M., Geschwind D., Børglum A.D., Robinson E., Grove J., Martin H., Bourgeron T., Baron-Cohen S.

A cross-disorder dosage sensitivity map of the human genome. Collins R.L., Glessner J.T., Porcu E., Lepamets M., Brandon R., Lauricella C., Han L., Morley T., Niestroj L.-M., Ulirsch J., Everett S., Howrigan D.P., Boone P.M., Fu J., Karczewski K.J., Kellaris G., Lowther C., Lucente D., Mohajeri K., Nõukas M., Nuttle X., Samocha K.E., Trinh M., Ullah F., Võsa U., Epi25 Consortium, Estonian Biobank Research Team, Hurles M., Aradhya S., Davis E.E., Finucane H., Gusella J., Janze A., Katsanis N., Matyakhina L., Neale B.M., Sanders D., Warren S., Hodge J.C., Lal D., Ruderfer D.M., Meck J., Mägi R., Esko T., Reymond A., Kutalik Z., Hakonarson H., Sunyaev S., Brand H., Talkowski M.

Genome-wide transcriptome profiling reveals the functional impact of rare de novo and recurrent CNVs in autism spectrum disorder. Luo R., Sanders S., Tian Y., Voineagu I., Huang N., Chu S.H., Klei L., Cai C., Ou J., Lowe J.K., Hurles M., Devlin B., State M., Geschwind D.