De novo mutations in children born after medical assisted reproduction DOI Creative Commons

RM Smits,

Miguel J. Xavier, Manon S. Oud

и другие.

Human Reproduction, Год журнала: 2022, Номер 37(6), С. 1360 - 1369

Опубликована: Апрель 12, 2022

Abstract STUDY QUESTION Are there more de novo mutations (DNMs) present in the genomes of children born through medical assisted reproduction (MAR) compared to spontaneously conceived children? SUMMARY ANSWER In this pilot study, no statistically significant difference was observed number DNMs MAR versus children. WHAT IS KNOWN ALREADY are known play a major role sporadic disorders with reduced fitness such as severe developmental disorders, including intellectual disability and epilepsy. Advanced paternal age is place offspring at increased disease risk, amongst others by increasing their genome. There very few studies reporting on effect offspring, especially when male infertility be affecting potential fathers. With delayed parenthood an ongoing epidemiological trend 21st century, from fathers advanced every day. DESIGN, SIZE, DURATION This observational study conducted January 2015 March 2019 tertiary care centre Radboud University Medical Center. We included total 53 respective parents, forming 49 trios (mother, father child) two quartets siblings). One group after spontaneous conception (n = 18); second IVF 17) third ICSI combined testicular sperm extraction (ICSI-TESE) 18). we also subdivided each age, resulting subgroup younger (<35 years conception) older (>45 conception). PARTICIPANTS/MATERIALS, SETTING, METHODS Whole-genome sequencing (WGS) performed all parent-offspring identify DNMs. For 34 trios/quartets, WGS twice independently detect validate presence Quality WGS-based DNM calling assessed targeted Sanger sequencing. MAIN RESULTS AND THE ROLE OF CHANCE No differences were per child for different methods conception, independent parental (multi-factorial ANOVA, f(2) 0.17, P-value 0.85). As expected, clear adjusting method maternal (multiple regression model, t 5.636, 8.97 × 10−7), average 71 young age) 94 age). LIMITATIONS, REASONS FOR CAUTION other small-scale have recently reported contrasting results. Larger unbiased required confirm or falsify these WIDER IMPLICATIONS FINDINGS did not show genome offspring. Given that negative result good news ICSI-TESE children, if replicated larger cohort. FUNDING/COMPETING INTEREST(S) research funded Netherlands Organisation Scientific Research (918-15-667) Investigator Award Science Wellcome Trust (209451). The authors conflicts interest declare. TRIAL REGISTRATION NUMBER N/A.

Язык: Английский

Evolution of the SARS-CoV-2 Mutational Spectrum DOI Creative Commons
Jesse D. Bloom, Annabel C. Beichman, Richard A. Neher

и другие.

Molecular Biology and Evolution, Год журнала: 2023, Номер 40(4)

Опубликована: Апрель 1, 2023

Abstract SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, quantify the relative rates different types single-nucleotide mutations at 4-fold degenerate sites genome across millions human sequences. We find clear shifts several The most striking trend is a roughly 2-fold decrease rate G→T Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There also C→T Delta, and other subtle changes spectrum along phylogeny. speculate that these could arise from affect replication, packaging, antagonization host innate-immune factors, although environmental factors play role. Interestingly, more similar than earlier clades to shaped long-term evolution sarbecoviruses. Overall, our work shows dynamic variable suggests may be trending toward animal

Язык: Английский

Процитировано

51
Genetic variation across and within individuals DOI
Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin

и другие.

Nature Reviews Genetics, Год журнала: 2024, Номер 25(8), С. 548 - 562

Опубликована: Март 28, 2024

Язык: Английский

Процитировано

22
Generation of a Commercial-Scale Founder Population of Porcine Reproductive and Respiratory Syndrome Virus Resistant Pigs Using CRISPR-Cas DOI
Brian T. Burger, Benjamin P. Beaton, Matthew A. Campbell

и другие.

The CRISPR Journal, Год журнала: 2024, Номер 7(1), С. 12 - 28

Опубликована: Фев. 1, 2024

Disease resistance genes in livestock provide health benefits to animals and opportunities for farmers meet the growing demand affordable, high-quality protein. Previously, researchers used gene editing modify porcine CD163 demonstrated a harmful virus that causes reproductive respiratory syndrome (PRRS). To maximize potential benefits, this disease trait needs be present commercially relevant breeding populations multiplication distribution of pigs. Toward goal, first-of-its-kind, scaled program was established introduce single modified allele into four genetically diverse, elite lines. This effort produced healthy pigs resisted PRRS infection as determined by macrophage animal challenges. founder population will additional testing, multiplication, commercial upon regulatory approval. Applying CRISPR-Cas eliminate viral represents major step toward improving health.

Язык: Английский

Процитировано

19
The impact of paternal age on new mutations and disease in the next generation DOI
K Wood, Anne Goriely

Fertility and Sterility, Год журнала: 2022, Номер 118(6), С. 1001 - 1012

Опубликована: Ноя. 6, 2022

Язык: Английский

Процитировано

40
Inheritance of paternal DNA damage by histone-mediated repair restriction DOI Creative Commons
Siyao Wang, David H. Meyer, Björn Schumacher

и другие.

Nature, Год журнала: 2022, Номер 613(7943), С. 365 - 374

Опубликована: Дек. 21, 2022

How paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question biology. In humans, nearly 80% of transmitted mutations arise germline1, but transgenerational effects remained controversial mechanisms are unknown. Here we show that sex-separated Caenorhabditis elegans strains, paternal, not maternal, leads embryonic lethality. The irradiated males displayed various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement aneuploidy. Paternal double strand breaks were repaired by maternally provided error-prone polymerase theta-mediated end joining. Mechanistically, depletion an orthologue human histone H1.0, HIS-24, or heterochromatin protein HPL-1, could significantly reverse Removal HIS-24 HPL-1 reduced 3 lysine 9 dimethylation enabled error-free homologous recombination repair germline F1 generation from radiation-treated P0 males, consequently improving viability F2 generation. This work establishes mechanistic underpinnings heritable consequences on health offspring, which may lead congenital disorders cancer humans.

Язык: Английский

Процитировано

38
Experimental estimates of germline mutation rate in eukaryotes: a phylogenetic meta-analysis DOI Creative Commons
Yiguan Wang, Darren J. Obbard

Evolution Letters, Год журнала: 2023, Номер 7(4), С. 216 - 226

Опубликована: Июнь 19, 2023

Mutation is the ultimate source of all genetic variation, and over last 10 years ready availability whole-genome sequencing has permitted direct estimation mutation rate for many non-model species across tree life. In this meta-analysis, we make a comprehensive search literature estimates in eukaryotes, identifying 140 accumulation (MA) parent-offspring (PO) studies covering 134 species. Based on these data, revisit differences single-nucleotide (SNM) between different phylogenetic lineages update known relationships generation time, genome size, nucleotide diversity-while accounting nonindependence. We do not find significant difference MA PO estimated rates, but confirm that mammal plant have higher rates than arthropods unicellular eukaryotes lowest rates. are with longer times larger sizes, even when relationships. Moreover, although diversity positively correlated rate, gradient relationship significantly less one (on logarithmic scale), consistent populations smaller effective size. For 29 which data available, indel short deletions generally more common insertions. Nevertheless, despite recent progress, no either SNM or available majority deeply branching eukaryotic lineages-or most animal phyla. Even among charismatic megafauna, experimental remain unknown amphibia scarce reptiles fish.

Язык: Английский

Процитировано

36
Tracking the Evolution of Therapy-Related Myeloid Neoplasms Using Chemotherapy Signatures DOI
Benjamin Diamond, Bachisio Ziccheddu, Kylee Maclachlan

и другие.

Blood, Год журнала: 2023, Номер unknown

Опубликована: Янв. 10, 2023

Язык: Английский

Процитировано

26
Variation in mutation, recombination, and transposition rates inDrosophila melanogasterandDrosophila simulans DOI Creative Commons
Yiguan Wang,

Paul McNeil,

R. Abdulazeez

и другие.

Genome Research, Год журнала: 2023, Номер 33(4), С. 587 - 598

Опубликована: Апрель 1, 2023

The rates of mutation, recombination, and transposition are core parameters in models evolution. They impact genetic diversity, responses to ongoing selection, levels load. However, even for key evolutionary model species such as Drosophila melanogaster simulans, few estimates these available, we have little idea how vary between individuals, sexes, or populations. Knowledge this variation is fundamental parameterizing genome Here, provide direct their a West African European population D. simulans Across 89 flies, observe 58 single-nucleotide mutations, 286 crossovers, transposable element (TE) insertions. Compared the melanogaster, find has lower mutation rate (1.67 × 10-9 site-1 gen-1 vs. 4.86 gen-1) (8.99 10-5 copy-1 23.36 gen-1), but higher recombination (3.44 cM/Mb 2.06 cM/Mb). similar significantly lower, not different, rate. Overall, paternal-derived mutations more frequent than maternal ones both species. Our study quantifies among different populations our will benefit future studies genetics.

Язык: Английский

Процитировано

26
Genetic links between ovarian ageing, cancer risk and de novo mutation rates DOI Creative Commons
Stasa Stankovic, Saleh Shekari, Qin Qin Huang

и другие.

Nature, Год журнала: 2024, Номер 633(8030), С. 608 - 614

Опубликована: Сен. 11, 2024

Язык: Английский

Процитировано

13
DNA damage in testicular germ cells and spermatozoa. When and how is it induced? How should we measure it? What does it mean? DOI Creative Commons
R. John Aitken,

Sheena E.M. Lewis

Andrology, Год журнала: 2023, Номер 11(8), С. 1545 - 1557

Опубликована: Янв. 6, 2023

This review surveys the causes and consequences of DNA damage in male germ line from spermatogonial stem cells to fully differentiated spermatozoa. Within cell population, integrity is well maintained as a result excellent surveillance repair; however, progressive increase background mutation rates does occur with paternal age possibly aberrant repair replication error. Once has committed spermatogenesis, it responds genetic via range pathways or, if this process fails, by induction apoptosis. When fully-differentiated spermatozoa are stressed, they also activate truncated intrinsic apoptotic pathway which results activation nucleases mitochondria cytoplasm; physical architecture these prevents enzymes translocating nucleus induce fragmentation. Conversely, hydrogen peroxide released sperm midpiece during apoptosis able penetrate damage. The base excision such cleaving oxidized bases DNA, leaving abasic sites that alkali-labile readily detected comet assay. As levels oxidative stress enter perimortem, topoisomerase integrated into chromatin becomes activated SUMOylation. Such may initially facilitate reannealing double strand breaks but ultimately prepares for destruction reproductive tract. lesions found live mutagenic mutational load carried offspring, particularly context assisted conception. A variety strategies described managing patients expressing high their spermatozoa, reduce risks might pose offspring health.

Язык: Английский

Процитировано

22