講演情報
[O2-2]染色体複雑構造異常の切断点形成におけるクロマチンドメインの効果
○稲垣 秀人1, 加藤 武馬1, 豊田 敦2, 蒔田 芳男3, 倉橋 浩樹1 (1.藤田医科大学 医科学研究センター 分子遺伝学研究部門, 2.国立遺伝学研究所 比較ゲノム解析研究室, 3.旭川医科大学病院 遺伝子診療カウンセリング室)
The next generation sequencing technologies provide us novel views of chromosomes in the cells, such as interactions of the chromosomes, or chromosome conformations in nuclei. We analyzed an autism patient carrying a complex chromosomal rearrangement of 1, 2, 14 and Yq12 repeated region. Pacbio Sequel system successfully identified more than 40 breakpoint junctions. Yq12 shattered fragments as well as chromosome 2 and 14p fragments from ribosomal DNA repeats, ranging within 100 kb, were incorporated randomly into chromosome 1 and 2 breakpoints, representing a chromothripsis-like phenomenon. Most breakpoints were mapped in gene bodies in both chromosomes 1 and 2. In addition, the breakpoints in chromosome 2 were found to be clustered in three regions, 2p22.1, 2p21, and 2p16.3. In each cluster, breakpoints were located within a single topologically associated domain, suggesting the fragmented breakage occurred in chromatin domain-dependent manner. On the other hand, such clustered manner was not found in chromosome 1 breakpoints. When the breakpoints in both chromosomes 1 and 2 were mapped with the ENCODE regulation tracks in UCSC web site, most of the breakpoints or breakpoints clusters were near the histone mark, H3K27Ac peaks in many cell types. Since the Yq12 repeat region was reported to be specifically transcribed in male germ cells, all the fragmentation including Yq12 likely are transcription-dependent phenomenon. The results suggest that a subset of complex chromosomal rearrangements is related to the transcription, or chromatin states, possibly in spermatogenesis.