Genome-wide CNV array analysis in parent-offspring pairs with Moyamoya disease with and without clinical anticipation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Hokkaido University
• Principal Investigator: Yoshimoto Tetsuyuki 北海道大学, 医学(系)研究科(研究院), 客員研究員 (50647493)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA NAOKI 北海道大学, 医学(系)研究科(研究院), 講師 (40421961) ; KAZUMATA KEN 北海道大学, 大学病院, 講師 (60634144) ; SHICHINOHE HIDEO 北海道大学, 医学(系)研究科(研究院), 特任助教 (80374479) ; HOUKIN KIYOHIRO 北海道大学, 大学病院, 教授 (90229146) ; SASAKI HIDENAO 北海道大学, 医学(系)研究科(研究院), 教授 (80281806) ; ITO MASAKI 北海道大学, 大学病院, 医員 (10399850)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 家族性もやもや病 / 表現促進現象 / 遺伝子コピー数多型

Outline of Final Research Achievements

Copy Number Variation (CNV) defining a DNA segment 100 kilobases or larger in size and present at variable copy numbers in comparison with a reference genome were investigated in unbiased 15 parent-offspring pairs with Moyamoya disease (MMD). Clinical anticipation, defining that pediatric patient(s) were born from adult-onset parent(s), was confirmed in 10 pairs. Genome-wide CNV array analysis detected 211 CNV loci throughout the genome except for chr.21. Of these, overlapping CNV loci for more than 3 individuals were seen in 10 segments in autosomes. CNV in a region of chr16p13.3 was a unique locus, in which copy number state between each parent and offspring pairs varied. Notably for this CNV, copy number gain was observed in the offspring with anticipation compared to the parents. Copy number gain on chr16p13.3, containing 14 genes, may contribute to the anticipation of familial MMD by altering gene dosage in variable possible forms, although further validation is necessary.

Free Research Field

脳血管障害学