Dissertation
Dissertation > Medicine, health > Oncology > Nervous system tumors > Intracranial tumors and brain tumors

Candidate Genes of Familial Intracranial Aneurysm in a Chinese Han Family

Author ChengFeiFei
Tutor CaiYiLing
School Anhui Medical University,
Course Neurology
Keywords intracranial aneurysm candidate gene linkage analysis
CLC R739.41
Type Master's thesis
Year 2013
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Background and ObjectiveIntracranial aneurysm(IA) is characterized by an abnormal bulging of an artery in the brain, which most commonly develops in cerebral arterial bifurcation. It will lead to spontaneous subarachnoid hemorrhage(sSAH) with poor prognosis when intracranial aneurysm ruptures. Until now, the exact etiology of intracranial aneurysms formation remains unclear. In addition to ambiental factors, epidemiological studies have demonstrated a familial influence contributing to the pathogenesis of intracranial aneurysms. Molecular genetics study suggest that IA exhibits genetic heterogeneity. Familial intracranial aneurysms (FIA) is defined as there are at least two of the first degree relatives with aneurysmal subarachnoid or an unruptured intracranial aneurysm. The incidence of IA was2%-5%. Once the intracranial aneurysm is bleeding, morbidity and mortality of SAH resulting from the rupture of IA is high.It is focus on the genetics of IA. Genetics and clinical studies in foreign countries have made great progresses in FIA, while few studies of FIA were reported in China. Candidate genes of FIA give the cues to molecular genetics mechanism of FIA and lead to the early diagnosis, prevention and treatment of IA. The discover of a family with intracranial aneurysm can offer good resource to the genetic research.This study made linkage analysis with some candidate genes reported in foreign countries of FIA in a Chinese Han family with intracranial aneurysm.The aim is to find the relationship between the family and the reported candidate genes and explore the candidate genes of this family. Materials and methodsWe collected a Chinese Han family with FIA, choose ANIB1-8which was defined by OMIM (Online Mendelian Inheritance in Man) and some candidate genes of FIA reported in studies:7q11.2,19q13,1p36.13-34.3,5p15.2-14.3,2p13,9p21,11q24-q25,14q23,13q14.12-21.1,17cen. We made linkage analysis in these candidate genes and one SNP was sequenced directly.Specimens The family is made up of40persons in4grades,24males and16females. The first and second generation had passed away. The third and fourth generation include31persons,20male and11female.19of the family members including2intracranial aneurysm patients participated in the study.Methods Genotyping analysis were performed by16shot tandem repeats (STR) microsatellite polymorphism markers and3single nucleotide polymorphism markers on19candidate genes/loci, which is related to intracranial aneurysm. SNP marker rs1333040was sequenced directly and whether existing mutation or not was screened.Results1No linkage was found in7q11.2、19q13、1p34.3-36.13、5p15.2-14.3、2p13、11q24-25and14q23in this family.2A7-cM region between SNP marker rs7983420and rs17054625in13q14.12-21.1and TNFRSF13B gene in17cen did not have linkaged to the pedigrees.3The rs1333040-T allele polymorphism on9p21was not associated with the onset in the FIA pedigrees.ConclusionsExcluding the relationship between the above candidate genes and the pedigrees, the pedgrees may have new causative genes.

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