The focus of our lab is the identification and characterization of genes responsible for complex, common human conditions. Our approaches are to map, clone, and evaluate expression of critical genes in informative families and populations. Because the conditions of interest to us are not purely genetic, we also study the interaction between genetic and environmental influences on human traits.
Genetic analysis of breast and ovarian cancer.
Current projects include 1) population genetics and epidemiology of
inherited variation in BRCA1 and BRCA2 (with Wylie Burke); 2) genomic basis of
variation of expression of BRCA1 (with Lee Hood); 3) construction of a murine
BRCA1 knockout and its characterization in different murine genetic backgrounds
(with Phil Soriano); 4) timing of alterations of BRCA1 expression in epithelial
cells during human breast carcinogenesis (with Charles Laird, Allan Gown, Roger
Moe and Ben Anderson); 5) possible role of mutations in the ataxia
telangiectasia gene in breast cancer susceptibility (with Pat Concannon); 6)
mapping of genes for inherited susceptibility to breast or ovarian cancer in
families not variant at BRCA1 or BRCA2.
Genetics of inherited deafness.
Although human deafness is
complex, there are rare families in whom hearing loss is purely genetic and
involves no other phenotype. Identification and characterization of the genes
responsible for nonsyndromic, inherited deafness would contribute to the
understanding of human deafness generally. We mapped postlingual deafness in an
extended kindred from Costa Rica with >200 informative relatives and are now
cloning the gene.
Human genetic variation in susceptibility to HIV 1 and AIDS.
Two epidemiologic features of the AIDS epidemic are that not everyone
exposed to HIV1 becomes infected, and that among HIV-infected individuals, the
rate of disease progression varies dramatically. We are investigating whether
naturally occurring variation in human immune response genes and/or in the HIV1
sequence influence progression of disease after infection with HIV1 among
infants infected in utero.
Population genetics of variation in mitochondrial DNA (mtDNA) sequences.
Human mtDNA is maternally inherited and includes highly polymorphic regions. We
have sequenced these highly variable regions in order to establish the
relatedness of individuals from the same maternal lineage. We are interested in
the specificity of mtDNA for the identification of maternal lineages and in
using mtDNA sequences to trace the movements of human populations.