Studies at the hemochromatosis (HFE) locus : gene conversions, haplotypes, and association analysis

Haplotype-based association studies offer an exciting potential methodology for the identification of genes that contribute to complex traits. There is thus great interest in understanding the biological forces that shape haplotypes. We have studied a well-characterized genetic locus surrounding the gene responsible for hereditary hemochromatosis (HFE) to investigate the impact of meiotic recombination events upon haplotype structure in this region. First we identified crossover hotspots in order to define the boundaries of haplotype blocks in this locus. We then found that gene conversion events play a significant role in shaping haplotype structure within these haplotype blocks. These gene conversion events were not limited to recombination hotspots and occurred with a frequency as high as 1 in 104 per site per generation. Gene conversions lead to the creation of new haplotypes and we suggest that they are important for the spread of disease alleles in a population. In addition, we discuss how these events can be used as important tools in haplotype-based association studies. We also present an association study in a large Venezuelan cohort to search for genes that contribute to residual age of onset in Huntington's disease. We demonstrate significant association between multiple alleles in a region on chromosome 6p21.3.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Kamihara-Ting, Junne

Advisor dc:contributor.advisor

• David E. Housman.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34193
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34193

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34193