Genome-wide identification of Chiari malformation type I associated candidate genes and chromosomal variations

Authors : Timucin AVSAR, Seyma CALİS, Baran YİLMAZ, Gulden DEMİRCİ OTLUOGLU, Can HOLYAVKİN, Turker KİLİC

Pages : 449-456

View : 18 | Download : 8

Publication Date : 2020-12-01

Article Type : Research Paper

Abstract :Chiari malformation type I insert ignore into journalissuearticles values(CMI); is a brain malformation that is characterized by herniation of the cerebellum into the spinal canal. Chiari malformation type I is highly heterogeneous; therefore, an accurate explanation of the pathogenesis of the disease is often not possible. Although some studies showed the role of genetics in CMI, the involvement of genetic variations in CMI pathogenesis has not been thoroughly elucidated. Therefore, in the current study we aim to reveal CMI-associated genomic variations in familial cases. Four CMI patients and 7 unaffected healthy members of two distinct families were analyzed. A microarray analysis of the affected and unaffected individuals from two Turkish families with CMI was conducted. Analyses of single nucleotide variations insert ignore into journalissuearticles values(SNVs); and copy number variations insert ignore into journalissuearticles values(CNVs); were performed by calculation of B allele frequency insert ignore into journalissuearticles values(BAF); and log R ratio insert ignore into journalissuearticles values(LRR); values from whole genome SNV data. Two missense variations, OLFML2A insert ignore into journalissuearticles values(rs7874348); and SLC4A9 insert ignore into journalissuearticles values(rs6860077);, and a 5’UTR variation of COL4A1 insert ignore into journalissuearticles values(rs9521687); were significantly associated with CMI. Moreover, 12 SNVs in the intronic regions of FAM155A, NR3C1, TRPC7, ASTN2, and TRAF1 were determined to be associated with CMI. The CNV analysis showed that the 11p15.4 chromosome region is inherited in one of the families. The use of familial studies to explain the molecular pathogenesis of complex diseases such as CMI is crucial. It has been suggested that variations in OLFML2A, SLC4A9, and COL4A1 play a role in CMI molecular pathogenesis. The CNV analysis of individuals in both families revealed a potential chromosomal region, 11p15.4, and risk regions that are associated with CMI.
Keywords : Chiari type I malformation, neurogenetics, microarray analysis, molecular karyotyping