Genetic studies of autistic disorder and chromosome 7
Genetic studies of autistic disorder and chromosome 7
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DOI：
10.1006/geno.1999.5968
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发表时间：
1999-11-01
期刊：
影响因子：
4.4
通讯作者：
Pericak-Vance, MA
中科院分区：
文献类型：
--
作者：
Ashley-Koch, A;Wolpert, CM;Pericak-Vance, MA
全基因组扫描表明，7 q上的一个位点参与了自闭症（AD）的病因。我们已经确定了一个II型AD家系，其中三个同胞从他们的母亲那里遗传了一个7号染色体候选区域（inv（7）（q22-q31.2））的旁着丝粒倒位。临床上，两个男性同胞患有AD，而女性同胞患有表达性语言障碍。母亲携带倒置，但不表达AD。该家族的单倍型数据表明，倒位的染色体起源来自孩子的外祖父。基于这些数据，我们对76个多重（大于或等于2个AD受影响/家族）家族的7 q区域标记进行了基因分型。两点连锁分析得出D 7S 495的最大异质性lod评分为1.47，最大lod评分（MLS）为1.03。多点MLS和NPL分析导致D 7S 2527的峰值评分为1.77，D 7S 640的峰值评分为2.01。检查受影响的同胞显示显着的父亲（P = 0.007），但不是母亲（P = 0.75），身份的血统共享在D 7S 640。显着的连锁不平衡，检测到父亲（P = 0.02），但不是母亲（P = 0.15），在D 7S 1824在多重和单胎家庭的传输。也有证据表明AD家族与非AD家族相比，该区域（D 7S 1817至D 7S 1824）的重组增加（P = 0.03，性别平均; P = 0.01，性别特异性）。这些结果进一步证明了染色体7 q上存在AD基因座，并表明该基因座可能是父系表达的。(C)北京：科学出版社.
Genome-wide scans have suggested that a locus on 7q is involved in the etiology of autistic disorder (AD). We have identified II AD family in which three sibs inherited from their mother a paracentric inversion in the chromosome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs have AD, while the female sib has expressive language disorder. The mother carries the inversion, but does not express AD. Haplotype data on the family suggest that the chromosomal origin of the inversion was from the children's maternal grandfather. Based on these data, we have genotyped 76 multiplex (greater than or equal to 2 AD affected/family) families for markers in this region of 7q. Two-point linkage analysis yielded a maximum heterogeneity lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoint MLS and NPL analyses resulted in peak scores of 1.77 at D7S2527 and 2.01 at D7S640. Examination of affected sibpairs revealed significant paternal (P = 0.007), but not maternal (P = 0.75), identity-by-descent sharing at D7S640. Significant linkage disequilibrium was detected with paternal (P = 0.02), but not maternal (P = 0.15), transmissions at D7S1824 in multiplex and singleton families. There was also evidence for an increase in recombination in the region (D7S1817 to D7S1824) in the AD families versus non-AD families (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results provide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expressed. (C) 1999 Academic Press.