Germ line origins of de novo mutations in hemophilia B families

ArthurR. Thompson; Shi-Han Chen

doi:10.1007/bf00208288

Detailed profiles of histone modification in male germ line cells of the young and aged mice

10.1101/635961 ◽

2019 ◽

Author(s):

Misako Tatehana ◽

Ryuichi Kimura ◽

Kentaro Mochizuki ◽

Noriko Osumi

Keyword(s):

Gene Expression ◽

Histone Modification ◽

Histone Modifications ◽

Sex Chromosomes ◽

De Novo ◽

Germ Line ◽

Epidemiological Studies ◽

De Novo Mutations ◽

Male Germ Line ◽

M Phase

Human epidemiological studies have shown paternal aging as one of the risks for neurodevelopmental disorders such as autism in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence biology of offspring. Here we are focusing on epigenetic alterations in sperm that can influence offspring developmental programs. In this study, we qualitatively and semi-quantitatively evaluated histone modification patterns in male germ line cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months) and aged (12 months) old mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, H3K9me3 was decreased in the male germ line cells in the aged testis, while H3K27me2/3 was increased. The intensity of H3K27ac, an active mark, was relatively low in the aged testis. Interestingly, H3K27ac was detected in putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germ line cells in the aged testis. H3K79me3 was contrastingly increased and accumulated on the sex chromosomes at M-phase spermatocytes. Therefore, aging induced alterations in the amount of histone modifications, of which patterns were different in individual histone modifications. Moreover, histone modification seems to be differentially regulated by aging on the sex chromosomes and on others. These findings would help elucidate epigenetic mechanisms underlying influence of paternal aging on offspring's development.

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Environmental Exposure of the Mouse Germ Line: DNA Adducts in Spermatozoa and Formation of De Novo Mutations during Spermatogenesis

PLoS ONE ◽

10.1371/journal.pone.0011349 ◽

2010 ◽

Vol 5 (6) ◽

pp. e11349 ◽

Cited By ~ 34

Author(s):

Ann-Karin Olsen ◽

Åshild Andreassen ◽

Rajinder Singh ◽

Richard Wiger ◽

Nur Duale ◽

...

Keyword(s):

Environmental Exposure ◽

Dna Adducts ◽

De Novo ◽

Germ Line ◽

De Novo Mutations

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Analysis of de novo germline genome mutations

Impact ◽

10.21820/23987073.2018.3.63 ◽

2018 ◽

Vol 2018 (3) ◽

pp. 63-65

Author(s):

Mizuki Ohno

Keyword(s):

Dna Sequences ◽

De Novo ◽

Germ Line ◽

Gene Mutations ◽

Germline Mutations ◽

Genetic Alterations ◽

Cellular Damage ◽

Base Sequence ◽

De Novo Mutations ◽

Basic Genome

Gene mutations are permanent alterations in sections of DNA sequences called genes. This causes a significant and distinguishable change in the base sequence of the affected DNA. They are changes to the base sequence that can occur spontaneously or in response to cellular damage and can vary greatly in size and position, ranging from a single base pair mutation, to changes that span segments of chromosomes, across several genes. Mutations in somatic (non-reproductive) cells are not passed on to the next generation, however germline mutations can occur in germ line cells that can produce egg and sperm, thus causing changes to the basic genome to become fixed in the DNA for future generations to come. This article focuses on germline mutations that are of particular interest to Ohno and her team. Many of these mutations - so called de novo mutations - are genetic alterations present for the first time in one family member as a result of a variation or mutation in a germ cell in either an egg or sperm of one of the parents. DNA repair systems allow for many of the mutations to be prevented and, in reality, only a low level of them become carried forward in the genome. Ohno and her team recognise the causes of germline mutation and are seeking to understand the implications of mutation, with a view to establishing how they may evolve and the possibilities for our future selves. The current human genome is a result of amassed mutations that have accumulated in our genome and driven it along certain pathways to yield what we are now. Ohno is currently working with gene-modified mice but the work is transferable to any mammalian genome, including humans to determine a possible future pathway.

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