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Mutation rate in sperm as males age - Coggle Diagram
Mutation rate in sperm as males age
The impact of chemo- and radiotherapy treatments on selfish de novo FGFR2 mutations in sperm of cancer survivors
study?
"selfish" mutation
mutations occur spontaneously in the sperm
increasing with age
Apert syndrome
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Crouzon syndromes
treatment from 18 men were compared to levels in pre-treatment samples
What effect does cancer treatment have on levels of spontaneous selfish FGFR2 mutations in human sperm?
does not increase level of spontaneous FGFR
reduce the level of disease associated (Apert syndrome) mutation in sperm
moderately-sterilizing alkylating regimens
results
within 3 years after therapy
spermatogenesis
similar to untreated controls
Group 3, n=4
methods
highly sensitive assay
4 different group on treatment
length and time for spermatogenesis recovery
DNA extracted from semen
Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring
background
over the last decade
effect of paternal age on semen quality
advancing paternal age
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increase risk of male infertility
testicular functions
increase risk of genetics disease
negative effects on sperm quality
DNA mutation
increase rate of preterm birth
interesting
the most of male have a first child at the later age
age of man
over 75 years old man
decrease # of sertoli cells
31% smaller mean testicular volume
age group 18-40
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The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect
spermatogonial stem cell
male germ cell production
higher mutation frequency
Sperm DNA from different ages
nucleotide substitution in fibroblast growth factor
FGF3 gene causes achondroplasia
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method
G1138A mutations in sperm DNA
sperm extracted used Puregene DNA isoltion kits
concentration and purity of sperm DNA
Evidence for Selective Advantage of Pathogenic FGFR2 Mutations in the Male Germ Line
males have high mutation rate than woman
methods
sensitive
nucleotide 755 fibroblast
recept 2 FGFR2 gene
PAE mutation
Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm
what study for?
advancing male age have multiple genomic defects in sperm
DNA fragmentation index
gene mutations
numerical chromosomal abnormalities
incidence of susceptible
nonsmoking group of 97 men
major association
sensitive of age
frequencies of sperm with DFI
fibroblast growth factor receptor 3 (FGFR3)gene mutation
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achondroplasia
Cellular evidence for selfish spermatogonial selection in aged human testes
delayed paternity
old father at high risk of their children
called paternal age effect (PAE)
achondroplasia
Apert syndrome
Costello syndrome
caused by specific mutations
gene coding components
tyrosine kinase
RAS
Elevated germline mutation rate in teenage fathers
study
analysed DNA from 24097 parents and their children
Europe
Middle and East Africa
father mutation rate have 7 times higher than mothers
surprising
teenage fathers have high mutation rate than teenage mothers
Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression
high risk factor in the offspring
neuodevelopmental psychiatric disorders
schizophrenia
autism spectrum disorders
compare sperm from young and old mice
old mice loss methylation
brain DNA methylation abnormal
In Utero Exposure to Benzo[a]Pyrene Increases Mutation Burden in the Soma
and Sperm of Adult Mice
mutation occur during embryonic
influence of environmental factors
mutation frequency increased
bone marrow
liver
brain
sperm
decreased sperm count
A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility
mature sperm are motile
have fully formed acrosome
glycosyltransferase-like gene, human polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5)
heterozygous mutation
affected male fertility
infertility syndome in humans
asthenozoospermia
disrupted protein loading into acrosomes
genetic mutation
In silico analysis of non-synonymous single nucleotide polymorphisms in human
DAZL gene associated with male infertility
most frequent type of genetics mutation
single nucleotide polymorphism (SNP)
spermatogenesis
haploid
deleted in azoospermia like (DAZL)
male infertility
decrease the sperm count
oligozoospermia
azoospermia
DO VARIATIONS IN SUBSTITUTION RATES AND MALE MUTATION BIAS CORRELATE WITH LIFE‐HISTORY TRAITS? A STUDY OF 32 MAMMALIAN GENOMES
life history affect substitution rate
32 mammalian genomes
study life history traits
increased generation time
strongest predictor of variation
substitution rate
male mutation bias
no significant correlation between
sperm competition
wither autosomal substitution rate
male mutation bias