Sponsors Taube Center for Jewish Studies Department of Biology

Transcription

1 Sponsors Taube Center for Jewish Studies Department of Biology Co- sponsors Center for Compara<ve Studies in Race and Ethnicity Ecology & Evolu<on Group, Department of Biology Morrison Ins<tute for Popula<on and Resource Studies Stanford Center for Popula<on Research, Ins<tute for Research in the Social Sciences Stanford Con<nuing Studies

2 Course themes Gene<c rela<onships among Jewish popula<ons Interac<ons between cultural and biological views about Jewish ancestry Origin and history of Jewish gene<c diseases

3

4

5 special issue (approx. Oct 2013) From Genera*on to Genera*on: the Gene*cs of Jewish Popula*ons Noah Rosenberg & Steve Weitzman, editors

6 Iden<fiability of Ashkenazi ancestry AC Need et al. (2009) Genome Biol 10: R7

7 Gene<c rela<onships among Jewish and non- Jewish popula<ons European and North African Jews Yemenite Jews Middle East and Caucasus Jews DM Behar et al. (2010) Nature 466:

8 Applica<ons of gene<c ancestry studies in Jewish popula<ons Historical popula<on migra<ons Endogamy in recent genera<ons Personal genomics Reducing confounding in gene<c disease associa<on studies Iden<fying unknown samples

9 Gene<c rela<onships among Jewish and non- Jewish popula<ons Jewish Middle Eastern European Rosenberg Lab NM Kopelman et al. (2009) BMC Genet 10:80

10 Popula<on gene<cs of human embryonic stem cell lines Number of posters at the 2010 conference of the Interna<onal Society for Stem Cell Research CT Sco^ et al. (2010) Nature Methods 7:

11 Popula<on gene<cs of human embryonic stem cell lines Orcadian N & W European Adygei Druze PalesAnian French Basque Italian/ Tuscan Sardinian Rosenberg Lab JT Mosher et al. (2010) N Engl J Med 362:

12 Popula<on gene<cs of human embryonic stem cell lines Number of posters at the 2010 conference of the Interna<onal Society for Stem Cell Research CT Sco^ et al. (2010) Nature Methods 7:

13 Course themes Gene<c rela<onships among Jewish popula<ons Interac<ons between cultural and biological views about Jewish ancestry Origin and history of Jewish gene<c diseases

14 Views of Jewish gene<cs affect reproduc<ve technologies

15 Culturally dis<nct popula<on may have co- occurred with a gene<cally dis<nc<ve type

16 Cultural associa<on with a disease enabled reduc<on of the disease frequency Annual number of Tay- Sachs cases in the United States and Canada MM Kaback et al. (2001) Adv Genet 44:

17 Course themes Gene<c rela<onships among Jewish popula<ons Interac<ons between cultural and biological views about Jewish ancestry Origin and history of Jewish gene<c diseases

18 Gene<c diseases in the Ashkenazi popula<on Bloom Syndrome Breast Cancer Colon Cancer Canavan Disease Deafness Cys<nuria Dysautonomia Factor XI Deficiency Familial Hyperinsulinism Familial Hypercholesterolemia Fanconi Anemia Type C Galactosidase Deficiency Gaucher Disease Glycogenesis type 7 Mucolipidosis type IV Niemann- Pick Disease Tarui Disease Tay- Sachs Disease Torsion Dystonia Parkinson Disease

19 Why does the Ashkenazi popula<on have so many diseases? Spurious consequence of racialized science during a key period in medical history Natural selec<on favoring unknown posi<ve effects of disease muta<ons Founder effects, endogamy, and consanguinity

20 Runs of homozygosity (ROH) and tracts of iden<ty- by- descent (IBD)

21 Runs of homozygosity are elevated by bo^lenecks and consanguinity Africa Middle East Europe Central/ South Asia East Asia Oceania Americas Rosenberg Lab TJ Pemberton et al. (2012) Am J Hum Genet 91:

22 Long runs of homozygosity are elevated by consanguineous unions Africa Middle East Europe Central/ South Asia East Asia Oceania Americas Rosenberg Lab TJ Pemberton et al. (2012) Am J Hum Genet 91:

23 Jewish popula<ons have elevated iden<ty by descent PopulaAon Measurement of pairwise genomic sharing (cm) Ashkenazi Jewish 23.0 Sardinian 12.4 Finnish 10.0 Tuscan 9.3 Italian 0.1 BM Henn et al. (2012) PLoS One 7: e34267

24 Jewish popula<ons have elevated iden<ty by descent CL Campbell et al. (2012) PNAS 109:

25 Why does the Ashkenazi popula<on have so many diseases? 1. The history of the Ashkenazi Jewish popula<on produced elevated genomic sharing 2. Genomic sharing predicts the occurrence of deleterious muta<ons 3. Some of those muta<ons are expected to be disease- causing, others to confer disease risk

26 Course themes Gene<c rela<onships among Jewish popula<ons Many Jewish popula<ons do share dis<nc<ve mul<variate gene<c signatures Interac<ons between cultural and biological views about Jewish ancestry Views on Jewish gene<cs ma^er to prac<cal personal decisions Origin and history of Jewish gene<c diseases Modern genomics provides a framework for explaining Jewish gene<c disease risks