Germline De Novo Mutations with Parent of Origin in WGS Trios

This study is part of the 'First 1,000 Days of Life and Beyond' study at the Inova Translational Medicine Institute. Whole-genome sequencing data from 1,291 parent-offspring trios was used to study the properties of clustered de novo mutations. The maternal clusters were found to be enriched in regions with accelerated maternal mutation rate and show distinct mutational signatures. For additional details, please refer to: "Germline de novo mutation clusters arise during oocyte aging in genomic regions with increased double-strand break incidence". Jakob M. Goldmann, Vladimir B. Seplyarskiy, Wendy S.W. Wong, Thierry Vilboux, Pieter B. Neerincx, Dale L. Bodian, Benjamin D. Solomon, Joris A. Veltman, John F. Deeken, Christian Gilissen, John E. Niederhuber. Nature Genetics. ]]> Inclusion Criteria for Mothers The mother is in good general health and pregnant Age: >/= 18 years The study is not race-restricted Exclusion Criteria for Mothers Blood Transfusion in the previous six months Cancer: in the last 5 years (except small cell) Inclusion Criteria for Fathers and Family Members Good general health Age: >/= 18 years The study is not race-restricted Exclusion Criteria for Fathers and Family Members Non-paternity (if discovered through genotyping, father samples will be silently dropped from the study as described in the informed consent but longitudinal information will be continued to be gathered) Cancer: in the last 5 years (except small cell) ]]>本研究为英诺瓦转化医学研究所（Inova Translational Medicine Institute）开展的"生命最初1000天及后续"研究项目的组成部分。研究采用1291例亲子三人组（parent-offspring trios）的全基因组测序（Whole-genome sequencing）数据，对簇状新发突变（clustered de novo mutations）的特性展开探究。结果发现，母源突变簇富集于母源突变率加速的基因组区域，并展现出独特的突变特征。更多详细信息可参阅论文：《生殖系新发突变簇在双链断裂发生率升高的基因组区域中于卵母细胞衰老过程中形成（Germline de novo mutation clusters arise during oocyte aging in genomic regions with increased double-strand break incidence）》，作者为Jakob M. Goldmann、Vladimir B. Seplyarskiy、Wendy S.W. Wong、Thierry Vilboux、Pieter B. Neerincx、Dale L. Bodian、Benjamin D. Solomon、Joris A. Veltman、John F. Deeken、Christian Gilissen、John E. Niederhuber，发表于《自然·遗传学（Nature Genetics）》。 ### 母亲纳入标准 1. 整体健康状况良好且处于妊娠期； 2. 年龄≥18周岁； 3. 本研究无种族限制。 ### 母亲排除标准 1. 近6个月内接受过输血； 2. 近5年内罹患癌症（小细胞癌除外）。 ### 父亲及其他家庭成员纳入标准 1. 整体健康状况良好； 2. 年龄≥18周岁； 3. 本研究无种族限制。 ### 父亲及其他家庭成员排除标准 1. 非生父关系（若通过基因分型确认存在非生父情况，将按照知情同意书的约定静默剔除该父亲样本，但仍将继续收集相关纵向随访信息）； 2. 近5年内罹患癌症（小细胞癌除外）。