GENETIC-LINKAGE MAPPING FOR A SUSCEPTIBILITY LOCUS TO BIPOLAR ILLNESS - CHROMOSOME-2, CHROMOSOME-3, CHROMOSOME-4, CHROMOSOME-7, CHROMOSOME-9, CHROMOSOME-10P, CHROMOSOME-11P, CHROMOSOME-22, AND CHROMOSOME-XPTER

被引:44
作者
DETERAWADLEIGH, SD
HSIEH, WT
BERRETTINI, WH
GOLDIN, LR
ROLLINS, DY
MUNIEC, D
GREWAL, R
GUROFF, JJ
TURNER, G
COFFMAN, D
BARRICK, J
MILLS, K
MURRAY, J
DONOHUE, SJ
KLEIN, DC
SANDERS, J
NURNBERGER, JI
GERSHON, ES
机构
[1] THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT,PHILADELPHIA,PA 19107
[2] UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242
[3] UNIV HOUSTON,SCH MED,HOUSTON,TX
[4] INDIANA UNIV,MED CTR,INST PSYCHIAT RES,INDIANAPOLIS,IN
来源
AMERICAN JOURNAL OF MEDICAL GENETICS | 1994年 / 54卷 / 03期
关键词
MANIC-DEPRESSIVE; POLYMORPHISM; GENOTYPE; DOMINANT MODEL;
D O I
10.1002/ajmg.1320540307
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at Theta = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at Theta = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage but for PLANH1, at the weighting functions f(p)=1 and f(p)=1/sqrt(p) borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of <-2 at Theta = 0.01 were found. (C) 1994 Wiley-Liss, Inc.
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页码:206 / 218
页数:13
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