Dr Hilary Martin | Group leader

Martin, Hilary

My work focuses on the analysis of high-throughput sequence and genotype data from large cohorts to address various medical and population genetic questions.

I recently became a Group Leader in Human Genetics (September 2018). My new group will study population and medical genetics in populations with high consanguinity, to learn about genetic architecture of different traits and how demography and selection have shaped the distribution of disease-causing variation in these populations.

As a postdoc at Sanger, my major focus was on exploring genetic architecture in the Deciphering Developmental Disorders (DDD) study, a large cohort of exome-sequenced individuals with rare developmental disorders. I quantified the contribution of recessive coding variats to the cohort and found that they account for a surprisingly small fraction of patients (Figure 1; see our recent paper in Science). I also worked closely with Mari Niemi and Jeff Barrett on the role of common variation in the DDD. In this paper in Nature, we demonstrated that the same common SNPs that contribute to psychiatric traits and cognition in the general population also increase risk of these rare disorders generally thought to be monogenic. Future work will include exploring the contribution of more complex genetic architectures in these rare disorders, and the interplay between common and rare variants.

Contribution of recessive and de novo dominant coding variants to different groups of probands within the DDD study.
Estimates of the contribution of recessive and de novo dominant coding variants to different groups of probands within the DDD study, in either known or as-yet-undiscovered genes.

Levels of autozygosity in the East London Genes and Health cohort, stratified by ancestry and reported parental relatedness.
Levels of autozygosity in the East London Genes and Health cohort, stratified by ancestry and reported parental relatedness.

Additionally, as part of the East London Genes and Health Project, I am analysing exome-sequence data from British South Asian individuals with high levels of parental relatedness. These individuals are highly enriched for homozygous loss-of-function mutations that can be informative about gene function and, potentially, new drug targets, and we are piloting recall-by-genotype studies to investigate some of these. They also have high rates of certain complex diseases (e.g. type 2 diabetes), and we are investigating the genetic architecture of these diseases compared to European populations.

I did my PhD in the Donnelly group at the Wellcome Trust Centre for Human Genetics in Oxford, where I worked on an eclectic set of projects. As part of the WGS500 project (clinical whole-genome sequencing of various disorders), I analysed data from families with severe neurological diseases, and also evaluated different approaches for pinpointing causal mutations. I also conducted a meta-analysis of multiple cohorts in order to address the effect of maternal age on recombination rates, which had previously been controversial. Finally, I worked on population sequencing study of the platypus to investigate the population structure and history of this unique species, as well as its ten sex chromosomes.

Publications

  • Common genetic variants contribute to risk of rare severe neurodevelopmental disorders.

    Niemi MEK, Martin HC, Rice DL, Gallone G, Gordon S et al.

    Nature 2018;562;7726;268-271

  • A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes dramatically perturbed sleep patterns as well as intellectual disability.

    Davies B, Brown LA, Cais O, Watson J, Clayton AJ et al.

    Human molecular genetics 2017;26;20;3869-3882

  • Factors influencing success of clinical genome sequencing across a broad spectrum of disorders.

    Taylor JC, Martin HC, Lise S, Broxholme J, Cazier JB et al.

    Nature genetics 2015;47;7;717-726

  • Multicohort analysis of the maternal age effect on recombination.

    Martin HC, Christ R, Hussin JG, O'Connell J, Gordon S et al.

    Nature communications 2015;6;7846

  • Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

    Martin HC, Kim GE, Pagnamenta AT, Murakami Y, Carvill GL et al.

    Human molecular genetics 2014;23;12;3200-11

  • Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs.

    Martin HC, Wani S, Steptoe AL, Krishnan K, Nones K et al.

    Genome biology 2014;15;3;R51

  • Evolution of a membrane protein regulon in Saccharomyces.

    Martin HC, Roop JI, Schraiber JG, Hsu TY and Brem RB

    Molecular biology and evolution 2012;29;7;1747-56

  • A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes dramatically perturbed sleep patterns as well as intellectual disability.

    Davies B, Brown LA, Cais O, Watson J, Clayton AJ et al.

    Human molecular genetics 2017;26;20;3869-3882

  • Linear mixed model for heritability estimation that explicitly addresses environmental variation.

    Heckerman D, Gurdasani D, Kadie C, Pomilla C, Carstensen T et al.

    Proceedings of the National Academy of Sciences of the United States of America 2016;113;27;7377-82

  • Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.

    Mbarek H, Steinberg S, Nyholt DR, Gordon SD, Miller MB et al.

    American journal of human genetics 2016;98;5;898-908

  • Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

    van Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B et al.

    Clinical immunology (Orlando, Fla.) 2015;160;2;301-14

  • Multicohort analysis of the maternal age effect on recombination.

    Martin HC, Christ R, Hussin JG, O'Connell J, Gordon S et al.

    Nature communications 2015;6;7846

  • Factors influencing success of clinical genome sequencing across a broad spectrum of disorders.

    Taylor JC, Martin HC, Lise S, Broxholme J, Cazier JB et al.

    Nature genetics 2015;47;7;717-726

  • Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

    Martin HC, Kim GE, Pagnamenta AT, Murakami Y, Carvill GL et al.

    Human molecular genetics 2014;23;12;3200-11

  • Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs.

    Martin HC, Wani S, Steptoe AL, Krishnan K, Nones K et al.

    Genome biology 2014;15;3;R51

  • Evolution of a membrane protein regulon in Saccharomyces.

    Martin HC, Roop JI, Schraiber JG, Hsu TY and Brem RB

    Molecular biology and evolution 2012;29;7;1747-56

  • MicroRNAs and their isomiRs function cooperatively to target common biological pathways.

    Cloonan N, Wani S, Xu Q, Gu J, Lea K et al.

    Genome biology 2011;12;12;R126

  • Geographical genomics of human leukocyte gene expression variation in southern Morocco.

    Idaghdour Y, Czika W, Shianna KV, Lee SH, Visscher PM et al.

    Nature genetics 2010;42;1;62-7

Martin, Hilary
Hilary's Timeline
2018

started Group Leader position at Sanger

2016

started Research Fellowship at St John's College, Cambridge

started postdoc at Sanger

2015

finished PhD in Oxford

2011

started PhD at Wellcome Centre for Human Genetics, Oxford

finished BSc (Human Genetics) at the University of Queensland, Australia