An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.
An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.
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DOI：
10.1086/302803
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发表时间：
2000-03
影响因子：
9.8
通讯作者：
J. Vincent;M. Neves-Pereira;A. D. Paterson;Etsuko Yamamoto;Sagar V. Parikh;F. Macciardi;H. Gurling;S. Potkin;C. Pato;A. Macedo;M. Kovács;Marilyn A. Davies;J. Lieberman;H. Meltzer;A. Petronis;J. Kennedy
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文献类型：
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作者：
J. Vincent;M. Neves-Pereira;A. D. Paterson;Etsuko Yamamoto;Sagar V. Parikh;F. Macciardi;H. Gurling;S. Potkin;C. Pato;A. Macedo;M. Kovács;Marilyn A. Davies;J. Lieberman;H. Meltzer;A. Petronis;J. Kennedy
较大的CAG/CTG三核苷酸重复序列与精神分裂症（SCZ）和双相情感障碍（BPAD）与对照组相比，以前曾有报道，这意味着可能的病因作用，三核苷酸重复在这些疾病。两个不稳定的CAG/CTG重复序列，SEF 2 -1B和ERDA 1，最近被克隆，研究表明，大多数个体与大重复序列检测重复扩增检测（RED）在这些位点有大的重复等位基因。这些重复序列没有显示出大等位基因与BPAD或SCZ的关联。使用RED，我们已经鉴定出具有非常大的CAG/CTG重复的BPAD个体，其不是由于SEF 2 -1B或ERDA 1的扩增。从这个个体的DNA中，我们克隆了一个高度多态性的三核苷酸重复序列，由（CTA）n（CTG）n组成，在这个病人中非常长（约1,800 bp）。重复区域定位于染色体13 q21，在脆性位点FRA 13 C的1.2cM内。231例减数分裂中13例（5.6%）重复等位基因不稳定。在14个（1.在1,120例精神病、边缘型人格障碍或青少年抑郁症患者和710例健康对照者中，有5例（0.7%）。人类多态性研究中心（CEPH）参考家族1334也检测到非常大的等位基因。这种三联体扩增最近被报道是脊髓小脑共济失调8型（SCA 8）的原因，然而，我们的大等位基因以上的疾病阈值发生在个人无论是受SCA或已知的SCA家族史。在这个基因座的大等位基因的高频率是不一致的SCA 8的罕见发生。因此，似乎不太可能是扩张单独导致SCA 8;其他遗传机制可能是解释SCA 8病因所必需的。
Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.