A method for developing high-density SNP maps and its application at the type 1 angiotensin II receptor (AGTR1) locus

被引:12
作者
Antonellis, A
Rogus, JJ
Canani, LH
Makita, Y
Pezzolesi, MG
Nam, M
Ng, D
Moczulski, D
Warram, JH
Krolewski, AS [1 ]
机构
[1] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA
[3] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA
关键词
methods; polymorphism; sequence analysis; sequence alignment; genetic screening; linkage disequilibrium; genotype; variation; AGTR1; diabetic nephropathies;
D O I
10.1006/geno.2002.6713
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
Evaluating the potential genetic components of complex disease will likely be aided through the use of dense polymorphism maps. Previously, we reported evidence for linkage with diabetic nephropathy on chromosome 3q in a region encompassing the type I angiotensin 11 receptor (AGTR1) gene. To further investigate any role for this gene in disease onset, we set out to design a dense polymorphism map spanning the AGTR1 locus for the purpose of association studies. Toward this goal, we have developed a technique for rapid identification of polymorphisms in long stretches of genomic DNA. This approach uses long-range PCR, DNA pooling, and transposon-based DNA sequencing. Using this technique, we efficiently validated and genotyped 18 polymorphisms spanning the 60.5-kb AGTR1 locus. Our panel of polymorphisms has an average spacing of 3.2 kb and an average minor allele frequency of 24%.
引用
收藏
页码:326 / 332
页数:7
相关论文
共 18 条
[1]   APOE polymorphisms and the development of diabetic nephropathy in type 1 diabetes -: Results of case-control and family-based studies [J].
Araki, S ;
Moczulski, DK ;
Hanna, L ;
Scott, LJ ;
Warram, JH ;
Krolewski, AS .
DIABETES, 2000, 49 (12) :2190-2195
[2]  
Davidson LL, 1994, CHILD, V11, P3
[3]   Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM [J].
Doria, A ;
Onuma, T ;
Warram, JH ;
Krolewski, AS .
DIABETOLOGIA, 1997, 40 (11) :1293-1299
[4]   Characterization of polymorphisms in the promoter of the human angiotensin II subtype 1 (AT1) receptor gene [J].
Erdmann, J ;
Riedel, K ;
Rohde, K ;
Folgmann, I ;
Wienker, T ;
Fleck, E ;
Regitz-Zagrosek, V .
ANNALS OF HUMAN GENETICS, 1999, 63 :369-374
[5]   Single nucleotide polymorphisms as tools in human genetics [J].
Gray, IC ;
Campbell, DA ;
Spurr, NK .
HUMAN MOLECULAR GENETICS, 2000, 9 (16) :2403-2408
[6]   Linkage disequilibrium and the search for complex disease genes [J].
Jorde, LB .
GENOME RESEARCH, 2000, 10 (10) :1435-1444
[7]   Prospects for whole-genome linkage disequilibrium mapping of common disease genes [J].
Kruglyak, L .
NATURE GENETICS, 1999, 22 (02) :139-144
[8]   A general approach to single-nucleotide polymorphism discovery [J].
Marth, GT ;
Korf, I ;
Yandell, MD ;
Yeh, RT ;
Gu, ZJ ;
Zakeri, H ;
Stitziel, NO ;
Hillier, L ;
Kwok, PY ;
Gish, WR .
NATURE GENETICS, 1999, 23 (04) :452-456
[9]   SNPing away at complex diseases:: Analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease [J].
Martin, ER ;
Lai, EH ;
Gilbert, JR ;
Rogala, AR ;
Afshari, AJ ;
Riley, L ;
Finch, KL ;
Stevens, F ;
Livak, KJ ;
Slotterbeck, BD ;
Slifer, SH ;
Warren, LL ;
Conneally, PM ;
Schmechel, DE ;
Purvis, I ;
Pericak-Vance, MA ;
Roses, AD ;
Vance, JM .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (02) :383-394
[10]   Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q - Results of novel discordant sib-pair analysis [J].
Moczulski, DK ;
Rogus, JJ ;
Antonellis, A ;
Warram, JH ;
Krolewski, AS .
DIABETES, 1998, 47 (07) :1164-1169