Fine mapping of the 9q31 Hirschsprung's disease locus.
Fine mapping of the 9q31 Hirschsprung's disease locus.
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DOI：
10.1007/s00439-010-0813-8
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发表时间：
2010-06
期刊：
影响因子：
5.3
通讯作者：
Garcia-Barceló MM
中科院分区：
文献类型：
--
作者：
Tang CS;Sribudiani Y;Miao XP;de Vries AR;Burzynski G;So MT;Leon YY;Yip BH;Osinga J;Hui KJ;Verheij JB;Cherny SS;Tam PK;Sham PC;Hofstra RM;Garcia-Barceló MM
先天性巨结肠病（HSCR）是一种先天性疾病，其特征是在肠的不同长度处没有神经节。RET基因是主要的HSCR基因。RET突变的外显率降低和表型变异性表明该疾病涉及额外的修饰基因。在没有编码序列（CDS） RET突变的家族中，RET依赖修饰位点定位于9q31。然而，9q31致病位点尚待确定。为了精确定位9q31区域，我们对137个HSCR荷兰三人组的301个标签snp进行了基因分型，长度为7 Mb。这揭示了在173名中国HSCR患者和436名对照中，使用最近进行的全基因组关联研究获得的基因型数据进一步研究了两个hsc相关区域。在两个确定的区域之一中，SVEP1 snp被发现与荷兰HSCR患者在没有RET突变的情况下相关。这证实了在没有RET CDS突变的HSCR家族中与9q31区域的关联。然而，这一发现无法被复制。在中国，发现HSCR与IKBKAP相关。相比之下，这种关联在携带RET CDS突变的患者中更强，复制后p = 5.10 × 10−6 [OR = 3.32(1.99, 5.59)]。在中国人中发现IKBKAP与hsr相关，这表明人群特异性，并暗示RET突变携带者可能有额外的风险。我们的发现得到了IKBKAP在神经系统发育中的作用的支持。本文的在线版本（doi:10.1007/s00439-010-0813-8）包含补充材料，仅供授权用户使用。
Hirschsprung’s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 × 10−6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. The online version of this article (doi:10.1007/s00439-010-0813-8) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
EDERY, P;LYONNET, S;MUNNICH, A
通讯作者：
MUNNICH, A
DOI：
10.1073/pnas.0809630105
发表时间：
2009-02-24
影响因子：
11.1
作者：
Garcia-Barcelo, Maria-Merce;Tang, Clara Sze-man;Tam, Paul Kwong-hang
通讯作者：
Tam, Paul Kwong-hang
影响因子：
30.8
作者：
Carrasquillo, MM;McCallion, AS;Chakravarti, A
通讯作者：
Chakravarti, A
影响因子：
9.8
作者：
Brooks, AS;Bertoli-Avella, AM;Hofstra, RMW
通讯作者：
Hofstra, RMW
影响因子：
9.8
作者：
Burzynski, GM;Nolte, IM;Hofstra, RMW
通讯作者：
Hofstra, RMW