山东省孤独症全基因组扫描研究

doi:10.6040/j.issn.1671-7554.0.2014.554

摘要/Abstract

摘要： 目的通过全基因组扫描和关联分析,查找与孤独症相关联的遗传位点.方法选择美国应用生物系统公司(ABI)的Linkage Mapping Set 2.5套装试剂盒,用DNA混合池的方法对孤独症核心家系(患儿组与患儿父母组)和正常对照者(正常对照组)进行全基因组扫描;使用CLUMP软件和SPSS 12.0软件对等位基因频率进行比较.结果患儿组与正常对照组或患儿父母组在染色体1、4、7上的1p36.31、4q13.3、4q35.1、7p21.3区域的等位基因频率差异有统计学意义(P<0.01).结论山东省人群孤独症患者在1p36.31(D1S214)、4q13.3(D4S392)、4q35.1(D4S1535)、7p21.3(D7S513)区域存在关联位点.

关键词: 孤独症, DNA 混合池, 基因组, 遗传

Abstract: Objective To investigate the genetic loci associated with autism in the population of Shandong Province. Methods Linkage Mapping Set 2.5 including 400 microsatellite markers was used to screen 3 separated DNA pooling samples consisting of 38 autism children, their 75 parents and 1 000 normal controls. CLUMP and SPSS12.0 software were adopted for statistic analysis to compare the difference in allele frequency of each locus between autism children and controls, autism children and parents respectively. Results Significant differences in allele frequency were found at 1p36.31, 4q13.3, 4q35.1 and 7p21.3. Conclusion Genetic loci 1p36.31, 4q13.3, 4q35.1 and 7p21.3 are detected to be associated with autism in the population of Shandong Province, and susceptibility genes may be located around these regions.

Key words: Genome, Genetics, Autism, DNA pooling

中图分类号:

R749.94

杨树林, 杨帆, 翟静, 刘金同, 张燕, 陈刚. 山东省孤独症全基因组扫描研究[J]. 山东大学学报（医学版）, 2014, 52(11): 92-96.

YANG Shulin, YANG Fan, ZHAI Jing, LIU Jintong, ZHANG Yan, CHEN Gang. Genome-wide association study of autism in Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(11): 92-96.

参考文献

[1] 杨树林, 陈刚. 孤独症遗传学研究进展[J]. 精神医学杂志, 2009, 22(1):60-65. YANG Shulin, CHEN Gang. Advances in the genetics of autism [J]. Journal of Psychiatry, 2009, 22(1):60-65.
[2] 吴柏林, 邹小兵, 徐秀.孤独症:从基因组学到临床实践[J]. 中国循证儿科杂志, 2008, 3(4):241-246. WU Bailin, ZOU Xiaobing, XU Xiu. Autism:From genomics to clinical practice [J]. Chin J Evid Based Pediat, 2008, 3(4):241-246.
[3] 武丽杰. 我国孤独症谱系障碍流行病学现状及趋势[J]. 中国实用儿科杂志, 2013, 28(8):571-576. WU Lijie. The present situation and trend of the epidemiology of autism spectrum disorders in China[J]. Chinese Journal of Practical Pediatrics Aug, 2013, 28(8):571-576.
[4] Barcellos L F, Klitz W, Field L L, et al. Association mapping of disease loci, by use of a pooled DNA genomic screen [J]. Am J Hum Genet, 1997, 61(3):734-747.
[5] Coraddu F, Lai M, Mancosu C, et al. A genome-wide screen for linkage disequilibrium in Sardinian multiple sclerosis[J]. J Neuroimmunol, 2003, 143(1-2):120-123.
[6] Goertsches R, Villoslada, Comabella M, et al. A genomic screen of Spanish multiple sclerosis patients reveals multiple loci associated with the disease [J]. J Neuroimmunol, 2003, 143(1-2):124-128.
[7] Jonasdottir A, Thorlacius T, Fossdal R, et al. A whole genome association study in Icelandic multiple sclerosis patients with 4804 markers [J]. J Neuroimmunol, 2003, 143(1-2):88-92.
[8] Laaksonen M, Jonasdottir A, Fossdal R, et al. A whole genome association study in Finnish multiple sclerosis patients with 3669 markers [J]. J Neuroimmunol, 2003, 143(1-2):70-73.
[9] Liguori M, Sawcer S, Setakis E, et al. A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population [J]. J Neuroimmunol, 2003, 143(1-2):97-100.
[10] Martins Silva B, Thorlacius T, Benediktsson K, et al. A whole genome association study in multiple sclerosis patients from north Portugal[J]. J Neuroimmunol, 2003, 143(1-2):116-119.
[11] Johnson M, Griffiths L R. A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach[J]. J Hum Genet, 2005, 50(12):607-610.
[12] 周鹏, 魏然, 温晓燕, 等. 山东半岛东部地区精神分裂症21号染色体基因扫描研究[J]. 山东精神医学, 2006, 19(4):241-244. ZHOU Peng, WEI Ran, WEN Xiaoyan, et al. Association mapping of schizophrenia loci on chromosome 21, by use of Pooled DNA genomic screen in easten Shandong peninsular [J]. Journal of Psychiatry, 2006, 19(4):241-244.
[13] 魏然, 周鹏, 温晓燕, 等. 山东半岛东部地区精神分裂症8号染色体基因扫描研究[J]. 中国神经精神疾病杂志, 2007, 33(2):77-81. WEI Ran, ZHOU Peng, WEN Xiaoyan, et al. The study on chromosome 8 of schizophrenia in eastern shandong peninsula [J]. Chin J Nerv Ment Di, 2007, 33(2):77-81.
[14] 王博, 张成, 林汝相, 等. 山东省原发性高血压1号染色体基因扫描[J]. 中华高血压杂志, 2008, 16(2):160-165. WANG Bo, ZHANG Cheng, LIN Ruxiang, et al. Mapping of Essential Hypertension Loci on Chromosome 1 by Use of Pooled DNA [J]. Chin J Hypertension, 2008, 16(2):160-165.
[15] 杨树林, 陈刚, 翟静, 等. 山东省孤独症7号染色体基因扫描研究[J]. 精神医学杂志, 2009, 22(1):1-4. YANG Shulin, CHEN Gang, ZHAI Jing, et al. Mapping of autism loci on chromosome7 by use of pooled DNA [J]. Journal of Psychiatry, 2009, 22(1):1-4.
[16] 栾萌, 陈刚, 周鹏, 等. 山东省双向情感障碍6号染色体基因扫描研究[J]. 精神医学杂志, 2010, 23(3):161-164. LUAN Meng, CHEN Gang, ZHOU Peng, et al. A search for susceptibility genetic loci to bipolar disorder on chromosome 6 [J]. Journal of Psychiatry, 2010, 23(3):161-164.
[17] 张凤国, 唐剑, 陈星, 等. 山东省981例精神分裂症患者全基因组关联分析研究[J]. 精神医学杂志, 2011, 24(6):401-404. ZHANG Fengguo, TANG Jian, CHEN Xing, et al. Genomewide association analysis of 981 schizophrenic patients in Shandong Province of China [J]. Journal of Psychiatry, 2011, 24(6):401-404.
[18] 杨树林, 杨帆, 翟静, 等. 山东省孤独症4号染色体基因扫描研究[J]. 精神医学杂志, 2014, 27(3):169-174. YANG Shulin, YANG Fan, ZHAI Jing, et al. Genescan of chromosome 4 in autistic nuclear families in Shandong province [J]. Journal of Psychiatry, 2014, 27(3):169-174.
[19] Risch N, Spiker D, Lotspeich L, et al. A genomic screen of autism:evidence for a multilocus etiology[J]. Am J Hum Genet, 1999, 65(2):493-507.
[20] Fradin D, Cheslack-Postava K, Ladd-Acosta C, et al. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs [J]. PLoS One, 2010, 5(9):e12513.doi:10.1371/journal.pone.0012513.
[21] Cho S C, Yoo H J, Park M, et al. Genome-wide association scan of korean autism spectrum disorders with language delay:a preliminary study[J]. Psychiatry Investig, 2011, 8(1):61-66.
[22] Bartlett C W, Hou L, Flax J F, et al. A genome scan for loci shared by autism spectrum disorder and language impairment[J]. Am J Psychiatry, 2014, 171(1):72-81.
[23] Coon H, Villalobos M E, Robison R J, et al. Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees [J]. Mol Autism, 2010, 1(1):8.doi:10.1186/2040-2392-1-8.

相关文章 15

[1]	杨宇凡,李悦,谢灏,林春华. 胆固醇水平与神经源性膀胱风险的因果关系[J]. 山东大学学报 (医学版), 2026, 64(5): 67-73.
[2]	杨静,张磊. 儿童早期多生态位病毒组解析:未分类噬菌体多样性及其宿主特征[J]. 山东大学学报 (医学版), 2026, 64(5): 116-124.
[3]	赵万霞,詹群璋,金婷,刘玉新,曲崇正,吴剑纯. 基于孟德尔随机化分析肠道菌群、血液代谢物和肥胖的因果关系[J]. 山东大学学报 (医学版), 2026, 64(4): 72-82.
[4]	吴志晓,赵红洋. 孟德尔随机化分析免疫细胞表型与孤独症谱系障碍的因果关联[J]. 山东大学学报 (医学版), 2026, 64(3): 83-92.
[5]	齐硕,刘可宇,徐展望,谭国庆,张强. 改良活检优化宏基因组二代测序腰椎间盘感染早期诊断策略[J]. 山东大学学报 (医学版), 2026, 64(2): 96-103.
[6]	杨贺旻,孙茂林,刘适,殷玥,张娜,张明龙. EGCG对孤独症小鼠小脑浦肯野细胞及行为学的影响[J]. 山东大学学报 (医学版), 2026, 64(1): 43-56.
[7]	王皓正,张文雄. Q热伴胸腹主动脉瘤支架植入术后感染1例并文献复习[J]. 山东大学学报 (医学版), 2026, 64(1): 126-130.
[8]	王珊,刘伟,冯强,范莹莹,刘海霞,段延华,温红玲,焦伯延. 2021年济宁市柯萨奇病毒A组6型分离株全基因组特征分析[J]. 山东大学学报 (医学版), 2025, 63(9): 92-101.
[9]	李千,杨帆,薛付忠. 基于多模态数据融合的多癌种风险预测模型[J]. 山东大学学报 (医学版), 2025, 63(8): 79-85.
[10]	葛雪,赵红艳. 疱疹病毒感染对重症肺炎患者临床预后及呼吸道微生态的影响[J]. 山东大学学报 (医学版), 2025, 63(6): 27-37.
[11]	黄馨,王梦雪,付书璠,张琦悦,徐力. 代谢综合征及其组分与消化系统恶性肿瘤的因果关联:两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(5): 86-94.
[12]	徐晶晶,王新起,张洋,许旺旺,高进. P2X7受体抑制剂对青春期创伤后应激障碍大鼠行为及肠道菌群的影响[J]. 山东大学学报 (医学版), 2025, 63(4): 1-9.
[13]	王小磊,方骏,王安,朱武晖,史光军. 两样本孟德尔随机化分析肠道菌群与肝外胆管癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(4): 44-50.
[14]	丁婷婷,刘浩辰. WNT10A双等位基因突变导致非综合征型先天缺牙1例的遗传学分析及文献复习[J]. 山东大学学报 (医学版), 2025, 63(3): 92-98.
[15]	杜艾家,张曼,陈鹤,王丽新,尚应殊. 微小RNA-1270靶向调控血管生成素样蛋白7抑制巨噬细胞炎症和脂质蓄积[J]. 山东大学学报 (医学版), 2025, 63(2): 1-9.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed