A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia.
A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia.
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DOI：
10.1093/schbul/sbaa161
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发表时间：
2021-04-29
影响因子：
6.6
通讯作者：
Inglehearn CF
中科院分区：
文献类型：
--
作者：
Mahmood T;El-Asrag ME;Poulter JA;Cardno AG;Tomlinson A;Ahmed S;Al-Amri A;Nazari J;Neill J;Chamali RS;Kiwan N;Ghuloum S;Alhaj HA;Randerson Moor J;Khan S;Al-Amin H;Johnson CA;Woodruff P;Wilkinson ID;Ali M;Clapcote SJ;Inglehearn CF
我们报告了一个精神分裂症分离的近亲家庭，其分离方式与一种罕见的部分隐性易感等位基因的隐性遗传一致。从两组兄弟姐妹之间的4次婚姻中，有6个后代被诊断为精神障碍。纯合性图谱显示，所有受影响的个体都共享染色体13 q22.2 -31.1上的6.1 Mb纯合区域，包含13个蛋白质编码基因。微卫星分析证实了纯合性的影响单倍型在12个进一步明显未受影响的家庭成员。精神病学报告表明，在这些人中有4人患有轻度精神疾病的内在表型。外显子组和基因组测序显示，在风险单倍型内没有潜在的致病性编码或结构变异。过滤具有<0.05的次要等位基因频率的非编码变体，鉴定出17种预测具有显著影响的变体，其中2种最显著的在SCEL基因内或邻近SCEL基因。受影响的纯合子血液的RNA测序显示NDFIP 2和SCEL的转录上调。与SCEL不同，NDFIP 2在脑中高度表达，并且参与决定T辅助细胞（Th）1型和Th 2型表型，这在以前与精神分裂症有关。
We report a consanguineous family in which schizophrenia segregates in a manner consistent with recessive inheritance of a rare, partial-penetrance susceptibility allele. From 4 marriages between 2 sets of siblings who are half first cousins, 6 offspring have diagnoses of psychotic disorder. Homozygosity mapping revealed a 6.1-Mb homozygous region on chromosome 13q22.2-31.1 shared by all affected individuals, containing 13 protein-coding genes. Microsatellite analysis confirmed homozygosity for the affected haplotype in 12 further apparently unaffected members of the family. Psychiatric reports suggested an endophenotype of milder psychiatric illness in 4 of these individuals. Exome and genome sequencing revealed no potentially pathogenic coding or structural variants within the risk haplotype. Filtering for noncoding variants with a minor allele frequency of <0.05 identified 17 variants predicted to have significant effects, the 2 most significant being within or adjacent to the SCEL gene. RNA sequencing of blood from an affected homozygote showed the upregulation of transcription from NDFIP2 and SCEL. NDFIP2 is highly expressed in brain, unlike SCEL, and is involved in determining T helper (Th) cell type 1 and Th2 phenotypes, which have previously been implicated with schizophrenia.
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DOI：
10.1073/pnas.96.10.5604
发表时间：
1999-05-11
影响因子：
11.1
作者：
Detera-Wadleigh, SD;Badner, JA;Gershon, ES
通讯作者：
Gershon, ES
影响因子：
2.6
作者：
Li, Melody;Milligan, Carol J.;Petrou, Steven
通讯作者：
Petrou, Steven
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Mansour, Hader;Fathi, Warda;Klei, Lambertus;Wood, Joel;Chowdari, Kodavali;Watson, Annie;Eissa, Ahmed;Elassy, Mai;Ali, Ibtihal;Salah, Hala;Yassin, Amal;Tobar, Salwa;El-Boraie, Hala;Gaafar, Hanan;Ibrahim, Nahed E.;Kandil, Kareem;El-Bahaei, Wafaa;El-Boraie, Osama;Alatrouny, Mohamed;El-Chennawi, Farha;Devlin, Bernie;Nimgaonkar, Vishwajit L.
通讯作者：
Nimgaonkar, Vishwajit L.
影响因子：
11
作者：
Homann, O. R.;Misura, K.;DeLisi, L. E.
通讯作者：
DeLisi, L. E.