Localized breakdown in linkage disequilibrium does not always predict sperm crossover hot spots in the human MHC class II region

被引：33

作者：

Kauppi, L

Stumpf, MPH

Jeffreys, AJ

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA

[2] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England

[3] Univ London Imperial Coll Sci & Technol, Ctr Bioinformat, Div Mol Biosci, London SW7 2AZ, England

来源：

GENOMICS | 2005年 / 86卷 / 01期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1016/j.ygeno.2005.03.011

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

To investigate the relationship between meiotic crossover hot spots and block-like linkage disequilibrium (LD), we have extended our high-resolution studies of the human MHC class II region to a 90-kb segment upstream of the HLA-DOA gene. LD blocks in this region are not as well defined as in the neighboring 210-kb DNA segment but do show two regions of LD breakdown in which coalescent analysis indicates substantial historical recombination. Sperm crossover analysis of one region revealed a novel localized hot spot similar in intensity and morphology to most other MHC hot spots. Crossovers at this hot spot are not obviously affected by a large insertion/deletion polymorphism near the hot spot. The second region of LD breakdown, within the DPB1 gene, shows an extremely low level of sperm crossover activity and does not contain a sperm crossover hot spot. These results highlight the complexity of LD patterns and the importance of experimentally verifying crossover hot spots. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：13 / 24

页数：12

共 52 条

[31]

McVean G, 2002, GENETICS, V160, P1231

[32] The fine-scale structure of recombination rate variation in the human genome [J].

McVean, GAT ;

Myers, SR ;

Hunt, S ;

Deloukas, P ;

Bentley, DR ;

Donnelly, P .

SCIENCE, 2004, 304 (5670) :581-584

[33] Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21 [J].

Patil, N ;

Berno, AJ ;

Hinds, DA ;

Barrett, WA ;

Doshi, JM ;

Hacker, CR ;

Kautzer, CR ;

Lee, DH ;

Marjoribanks, C ;

McDonough, DP ;

Nguyen, BTN ;

Norris, MC ;

Sheehan, JB ;

Shen, NP ;

Stern, D ;

Stokowski, RP ;

Thomas, DJ ;

Trulson, MO ;

Vyas, KR ;

Frazer, KA ;

Fodor, SPA ;

Cox, DR .

SCIENCE, 2001, 294 (5547) :1719-1723

[34] Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots [J].

Phillips, MS ;

Lawrence, R ;

Sachidanandam, R ;

Morris, AP ;

Balding, DJ ;

Donaldson, MA ;

Studebaker, JF ;

Ankener, WM ;

Alfisi, SV ;

Kuo, FS ;

Camisa, AL ;

Pazorov, V ;

Scott, KE ;

Carey, BJ ;

Faith, J ;

Katari, G ;

Bhatti, HA ;

Cyr, JM ;

Derohannessian, V ;

Elosua, C ;

Forman, AM ;

Grecco, NM ;

Hock, CR ;

Kuebler, JM ;

Lathrop, JA ;

Mockler, MA ;

Nachtman, EP ;

Restine, SL ;

Varde, SA ;

Hozza, MJ ;

Gelfand, CA ;

Broxholme, J ;

Abecasis, GR ;

Boyce-Jacino, MT ;

Cardon, LR .

NATURE GENETICS, 2003, 33 (03) :382-387

[35] Absence of the TAP2 human recombination hotspot in chimpanzees [J].

Ptak, SE ;

Roeder, AD ;

Stephens, M ;

Gilad, Y ;

Pääbo, S ;

Przeworski, M .

PLOS BIOLOGY, 2004, 2 (06) :849-855

[36] dbSNP: the NCBI database of genetic variation [J].

Sherry, ST ;

Ward, MH ;

Kholodov, M ;

Baker, J ;

Phan, L ;

Smigielski, EM ;

Sirotkin, K .

NUCLEIC ACIDS RESEARCH, 2001, 29 (01) :308-311

[37] HOTSPOTS OF HOMOLOGOUS RECOMBINATION IN MOUSE MEIOSIS [J].

SHIROISHI, T ;

KOIDE, T ;

YOSHINO, M ;

SAGAI, T ;

MORIWAKI, K .

ADVANCES IN BIOPHYSICS, VOL 31, 1995, 1995, 31 :119-132

[38] Recombination breakpoints in the human β-globin gene cluster [J].

Smith, RA ;

Ho, PJ ;

Clegg, JB ;

Kidd, JR ;

Thein, SL .

BLOOD, 1998, 92 (11) :4415-4421

[39] A comparison of Bayesian methods for haplotype reconstruction from population genotype data [J].

Stephens, M ;

Donnelly, P .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (05) :1162-1169

[40] A new statistical method for haplotype reconstruction from population data [J].

Stephens, M ;

Smith, NJ ;

Donnelly, P .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (04) :978-989

← 1 2 3 4 5 6 →