Combined Biological Sciences Meeting

Professor of Human Genomics
J. Craig Venter Institute (JCVI), San Diego, CA, USA

Abstract 

Human Genome Sequencing-relevance of defining the outer limits of human diversity for global health

The era of advanced technological development has dramatically impacted the ability to generate a complete human genome (DNA sequence). The importance of defining human genomes is paramount to determining the extent of clinically relevant human DNA variation. This variance is important for assessing disease risk, outcome and response to pharmaceutical drugs. The effort to define the extent to human diversity at the DNA level has been limited to recently diverged Western societies, limiting global understanding of disease. Human genome sequencing and specifically personalized genomics (the sequence of a single named individual) has been no exception. Although Africa is home to 1/6th of the world’s population, has the largest within continent population diversity and is believed to be the birthplace of all mankind, only a single unnamed African male representing the Yoruba people from Nigeria has been sequenced by 2010. In February we published the first personalized indigenous genome sequences in an attempt to define the extent of human variation in Southern Africa. We report the genomes of the Archbishop Desmond Tutu (Bantu heritage) and four Bushmen from the Kalahari desert (Khoisan heritage), as the most divergent genomes sequenced to date. Our data provides not only a glimpse into our ancient past as hunter-gatherers and sheds light into human transition and expansion as farmers, but importantly will contribute to defining human phenotypic characteristics. We describe over 1.3 million new DNA variants, which we have made freely available to be used to advance the global effort to define human disease.

Biography

Dr Vanessa Hayes completed her PhD in Groningen, The Netherlands and after working on genetic susceptibility to HIV/AIDS in South Africa moved to Australia in 2003. She headed a Cancer Genetics team first at the Garvan Institute for Medical Research and more recently at the Children's Cancer Institute Australia. Her contributions to a better understanding of the genetics of prostate cancer risk has awarded her the Premiers award for NSW Cancer Research Fellow 2007, the Australian Academy of Science Inaugural Gani medal for Human Genetics in 2008 and an Australian-American Fulbright Professional Scholarship in 2009. Her over-riding research interest in understanding how DNA sequence variation impacts human evolution and ultimately disease evolution, in particular the strong ethnic bias impacted prostate cancer risk and outcome, resulted in her recent publication (18 February 2010) of the Bushmen and Bantu genomes in the journal Nature. Using the next generation sequencing platforms, this work has contributed 1.3 Million new DNA variants to current databases.

Significant Awards

Professional Australian-American Fulbright Scholar (2009)

Inaugural Ruth Stephens Gani Medal for Human Genetics, Australian Academy of Science (2008)

NSW/ACT Young Tall Poppy Award for Science (2007)

Premier’s Award for Outstanding Cancer Research Fellow, Cancer Institute of New South Wales (2007)

Recent Publications

1.     Stone J, Gurrin LC, Hayes VM, Southey MC, Hopper JL, Byrnes GB.  Sibship analysis of associations between SNP haplotypes and a continuous trait with application to mammographic density.  Genetic Epidemiology (2010) 34(4):309-18.

2.     Patterson N, Petersen DC, van der Ross RE, Sudoyo H, Glashoff RH, Marzuki S, Reich D, Hayes VM. Genetic structure of a unique admixed population: implications for medical research. Human Molecular Genetics (2010) 19:411-419.

3.     Miller W, Wright SJ, Zhang Y, Schuster SC, Hayes VM. Optimization methods for selecting founder individuals for captive breeding or reintroduction of endangered species. Pacific Symposium on Biocomputing (2010) 2010:43-53.

4.     Ratan A, Zhang Y, Hayes VM, Schuster SC, Miller W. Calling SNPs without a reference sequence. BMC bioinformatics (2010) 11(1):130.

5.     Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani1 P, Tindall EA, Danko CG, Siang Teo W, Buboltz A, Zhang Z, Ma Q, Oosthuysen A, Steenkamp A, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM. Complete Khoisan and Bantu Genomes from Southern Africa. Nature (2010) 463(7283):943-7.

6.     Tindall EA, Hayes VM. Comprehensive sequence analysis of the human IL23A gene defines new variation content and a high rate of evolutionary conservation. DNA Research (2010) 17(2):117-22.

7.     Tindall EA, Hoang HN, Southey MC, English DR, Hopper JL, Giles GG, Severi G, Hayes VM. The 4q27 locus and familial prostate cancer risk. BMC Cancer (2010) 10(1):69.

8.     Tindall EA, Petersen DC, Nikolaysen S, Miller W, Schuster SC, Hayes VM. Interpretation of custom designed Illumina genotype cluster plots for targeted association studies and next-generation sequence validation. BMC Research Notes (2010) 3(1):39.

9.     Schuster SC, Hayes VM. Issues raised by use of ethnic-group names in genome study: Schuster and colleagues reply. Nature. 2010 Mar 25;464(7288):487; author reply 487.

10. Tindall EA, Hayes VM, Petersen DC. Inflammatory genetic markers of prostate cancer risk. Cancers (2010), 2:1198-220. [Review].

11. Tindall EA, Severi G, Hoang HN, Ma CS, Fernandez P, Southey MC, English DR, Hopper JL, Heyns CF, Tangye SG, Giles GG, Hayes VM. Comprehensive analysis of the cytokine rich 5q31 region suggests a role for IL-4 gene variants in prostate cancer risk. Carcinogenesis (2010), Apr 19. [Epub ahead of print].

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