Genomics for the world: Population genetics in the personal genome era

Car­los D. Bus­ta­mante, PhD, Pro­fes­sor, Depart­ment of Genet­ics, Stan­ford Uni­ver­sity School of Med­i­cine   Web­site  |  Pub­li­ca­tions  |  @cdbustamante

Abstract: Full sequenc­ing of indi­vid­ual human genomes has greatly expanded our under­stand­ing of human genetic vari­a­tion and pop­u­la­tion his­tory. Here, we present a sys­tem­atic analy­sis of 50 human genomes from 11 diverse global pop­u­la­tions sequenced at high cov­er­age. Our sam­ple includes 12 indi­vid­u­als of admixed ances­try that have vary­ing degrees of recent (within the last 500 years) African, Native Amer­i­can, and Euro­pean ances­try. We find over 21 mil­lion sin­gle nucleotide vari­ants that con­tribute to a 1.75-fold range in nucleotide het­erozy­gos­ity across diverse human genomes with a high of 1 het­erozy­gous site per kilo­base in West African genomes to a low of 0.57 het­erozy­gous sites per kilo­base in seg­ments inferred to have diploid Native Amer­i­can ances­try from the genomes of Mex­i­can and Puerto Rican indi­vid­u­als. We find evi­dence for all three con­ti­nen­tal ances­tries in the genomes of Mex­i­can, Puerto Rican, and African Amer­i­can pop­u­la­tions, and the genome wide sta­tis­tics are highly con­sis­tent across indi­vid­u­als from a pop­u­la­tion, once ances­try pro­por­tions have been accounted for. Using a gen­er­al­ized lin­ear model, we iden­tify sub­tle vari­a­tions across pop­u­la­tions in the pro­por­tion of neu­tral vs. dele­te­ri­ous vari­a­tion, and find that genome-wide sta­tis­tics vary in admixed pop­u­la­tions even once ances­try pro­por­tions have been fac­tored in.  We fur­ther infer that mul­ti­ple peri­ods of gene flow shaped the diver­sity of admixed pop­u­la­tions in the Amer­i­cas, with 70% of the Euro­pean ances­try in today’s African Amer­i­cans dat­ing back to Euro­pean gene flow hap­pen­ing only 7–8 gen­er­a­tions ago.

Bio: I am a pop­u­la­tion geneti­cist whose research focuses on ana­lyz­ing genome wide pat­terns of vari­a­tion within and between species to address fun­da­men­tal ques­tions in biol­ogy, anthro­pol­ogy, and medicine.

Dur­ing the past nine years as a fac­ulty mem­ber at Cor­nell and Stan­ford, I have trained 43 post-doctoral fel­lows and grad­u­ate stu­dents as pri­mary advi­sory. My group works on a vari­ety of organ­isms and model sys­tems rang­ing from humans and other pri­mates to domes­ti­cated plant and ani­mals. Much of our research is at the inter­face of com­pu­ta­tional biol­ogy, math­e­mat­i­cal genet­ics, and evo­lu­tion­ary genomics. Exam­ples of our research accom­plish­ments include:

• Devel­op­ing selec­tion maps of the human genome which pin­point rapidly evolv­ing genes as well as genomic regions sub­ject to strong selec­tive con­straint;
• Devel­op­ing a high-density map of genetic vari­a­tion in the dog genome and using it to iden­tify genomic regions under­ly­ing mor­pho­log­i­cal dif­fer­ences among domes­tic dog breeds;
• Inves­ti­gat­ing the fine scale genetic struc­ture of human pop­u­la­tions and its impli­ca­tion for genomic medicine.

Our cur­rent research focuses on human pop­u­la­tion genomics and global health includ­ing devel­op­ing sta­tis­ti­cal, com­pu­ta­tional, and genomic resources for enabling trans– and multi-ethnic genome-wide asso­ci­a­tion and med­ical sequenc­ing stud­ies of com­plex bio­med­ical traits. My lab has both dry and wet lab exper­tise and stu­dents and post-docs from diverse fields includ­ing: applied math, biostatistics/statistics, com­pu­ta­tional biology/bioinformatics, anthropology/evolutionary biol­ogy, and genetics/genomics.