Department of Genetics
Harvard Medical School
New Research Building, Room 260
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 432-7794
Fax: (617) 432-6306
Web Page: The McCarroll Lab Page
My group is interested in how the human genome varies in structure and sequence and in how this genetic variation influences molecular phenotypes in cells and disease risk in populations.
The human genome shows extensive variation in structure and copy number – even among apparently healthy individuals – with both rare and common alleles that involve deletions, duplications and inversions of long genomic segments(tens to hundreds of kilobases). Our work is revealing the extent to which this type of variation pervades human genomes and its relationships both to human population history and to human phenotypic variation. We use experimental approaches based on next-generation sequencing and microarrays anddevelop novel computational approaches for analyzing data.
Our studies of the relationships of human genome variation to diseaserisk keep leading us to influences of the non-protein-coding parts of the genome on phenotypic variation. For example, we recently discovered two common deletionalleles that influence human phenotypes (Crohn’s disease and body weight regulation) via regulatory effects on nearby genes. These and other results highlight the need for a much deeper understanding of the systems of molecules that mediate the effects of genetic variation on phenotype. We are beginning experimental efforts to develop a more systematic understanding of how regulatory polymorphism influences molecular phenotypes in human cells.
To enable these and other projects, we are developing new experimental technology that utilizes next-generation sequencing to assay copy-number variation (CNVs) and SNPs in large population and disease cohorts.
Our general approach is to use experimental and computational approaches in integrative ways, and to combine genome-scale surveys with focused experimental dissection of particular genomic loci that can help us understand biological systems, genome evolution and aspects of human population genetics.
I am a new faculty member in the Department of Genetics.
- McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, Shapero MH, deBakker PIW, Maller J, Kirby A, Elliott AL, Parkin M, Hubbell E, Webster T, Mei R, Veitch J, Collins PJ, Handsaker R, Lincoln S, Nizzari M, Blume J, Jones K, Rava R, Daly MJ, Gabriel SB, Altshuler DM. Integrated detection and population genetic analysis of SNPs and copy number variation. Nature Genetics 40:1166-74, 2008.
- McCarroll SA, Huett AS, Kuballa P, Chilewski S, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Rioux JD, Altshuler D, Daly MJ, Xavier RJ. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nature Genetics 40:1107-1112, 2008.
- McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett J, Dallaire S, Gabriel SB, Lee C, Daly MJ, Altshuler DM. Common deletion polymorphisms in the human genome. Nature Genetics 38: 86-92, 2006.
- McCarroll SA, Altshuler DM. Copy-number variation and association studies of human disease. Nature Genetics 39: S37-42, 2007.
BBS webpage updated 12/02/2009