Pregnancy Loss: From Cytogenetics to Genomics

Early pregnancy, Journal Year: 2025, Volume and Issue: unknown, P. 299 - 316

Published: April 16, 2025

Language: Английский

---

Candidate Genes in Pregnancy Loss

Early pregnancy, Journal Year: 2025, Volume and Issue: unknown, P. 110 - 121

Published: April 16, 2025

Language: Английский

---

Expanded Carrier Screening for Prevention of Genetic Recessive Diseases

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---

Conclusions

Published: Jan. 1, 2025

---

Sequence diversity lost in early pregnancy

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

Every generation, the human genome is shuffled during meiosis and a single fertilized egg gives rise to all of cells body1. Meiotic errors leading chromosomal abnormalities are known causes pregnancy loss2,3, but genetic aetiologies euploid loss remain largely unexplained4. Here we characterize sequence diversity in early through whole-genome sequencing 1,007 fetal samples 934 parental from 467 trios affected by (fetus, mother father). Sequenced genomes enabled us determine both meiotic origins abnormalities, detected half our set. It further assess de novo mutations on homologous chromosomes parents transmitting extra chromosomes, date them, revealing that 6.6% maternal occurred before sister chromatid formation oocytes. We find similar number as 9,651 adult trios, three times pathogenic small (<50 bp) variant genotypes cases compared with adults. Overall, findings indicate around 1 136 pregnancies lost due genotype fetus. Our results highlight vast pregnancy.

Language: Английский

---

A systematic review to assess the utility of genomic autopsy using exome or genome sequencing in cases of congenital anomalies and perinatal death

Genetics in Medicine, Journal Year: 2024, Volume and Issue: 26(7), P. 101159 - 101159

Published: May 3, 2024

Language: Английский

---

Whole Genome Sequencing in Prenatal Diagnostics: The Danish Approach to Guideline Formation and Implementation Within Public Healthcare

Prenatal Diagnosis, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

ABSTRACT Objective To describe the implementation of whole genome sequencing (WGS) in prenatal diagnostics and outline national guideline system facilitating this. Methods Clinical guidelines for WGS were developed implemented by Danish Fetal Medicine Society. Results Guidelines expert consensus following a review 75 studies. Diagnostic yield served as key factor prioritizing various phenotypes, improving diagnostic accuracy informing clinical decisions. Phenotypes include nuchal translucency ≥ 6.0 mm, multiple anomalies, skeletal dysplasia, neuromuscular diseases, non‐immune hydrops fetalis, central nervous malformations, congenital diaphragmatic hernia severe fetal growth restriction (< 3 SDs not explained placental insufficiency). Small regional variations exist indications, bioinformatics, funding, but is now routinely used nationwide these indications. Conclusion The Society's development, emphasizing gradual implementation, has supported relatively uniform integration into diagnostics.

Language: Английский

---

Implications of Genomic Newborn Screening for Infant Mortality

International Journal of Neonatal Screening, Journal Year: 2023, Volume and Issue: 9(1), P. 12 - 12

Published: Feb. 28, 2023

Technological advances and decreasing costs of genomic sequencing have paved the way for increased incorporation genomics into newborn screening (NBS). Genomic may complement current NBS laboratory analyses or be used as a first-tier tool to identify disorders not detected by approaches. As large proportion infant deaths occur in children with an underlying genetic disorder, earlier diagnosis these improve neonatal mortality rates. This lends additional layer ethical consideration regarding screening. We review understanding contributions explore potential implications expanded access

Language: Английский

---

Lethal phenotypes in Mendelian disorders

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 13, 2024

Essential genes are those whose function is required for cell proliferation and/or organism survival. A gene's intolerance to loss-of-function can be allocated within a spectrum, as opposed being considered binary feature, since this might essential at different stages of development, genetic backgrounds or other contexts. Existing resources that collect and characterise the essentiality status based on either assessment in human lines, embryonic postnatal viability evaluation model organisms, gene metrics such variation scores derived from population sequencing studies. There also several repositories available document phenotypic annotations rare disorders humans Online Mendelian Inheritance Man (OMIM) Human Phenotype Ontology (HPO) knowledgebases. This raises prospect able use clinical data, including lethality most severe manifestation, further our characterisation essentiality. Here we queried OMIM terms related classified all into categories, according earliest age death recorded associated disorders, prenatal no reports premature death. To showcase curated catalogue genes, developed Lethal Phenotypes Portal (https://lethalphenotypes.research.its.qmul.ac.uk), where explore relationships between these constraint lines mouse. Further analysis categories reveals differences mode inheritance physiological systems affected disease class. We highlight how similarity same category combined with family/group information used novel discovery. Finally, overlaps discrepancies lethal phenotypes observed mouse discuss potential explanations include transcriptional regulation, functional compensation molecular mechanisms. anticipate resource will aid clinicians diagnosis early conditions assist researchers investigating properties make development.

Language: Английский

---

Lethal phenotypes in Mendelian disorders

Genetics in Medicine, Journal Year: 2024, Volume and Issue: 26(7), P. 101141 - 101141

Published: April 15, 2024

Purpose: Existing resources that characterise the essentiality status of genes are based on either proliferation assessment in human cell lines, viability evaluation mouse knockouts, or constraint metrics derived from population sequencing studies.Several repositories document phenotypic annotations for rare disorders, however there is a lack comprehensive reporting lethal phenotypes.Methods: We queried Online Mendelian Inheritance Man terms related to lethality and classified all according earliest age death recorded associated prenatal no reports premature death.We characterised across these categories, examined evidence models explored how this information could be used novel gene discovery.Results: developed Lethal Phenotypes Portal showcase curated catalogue essential genes.Differences mode inheritance, physiological systems affected disease class were found different categories as well discrepancies between phenotypes observed human. Conclusion:We anticipate resource will aid clinicians diagnosis early conditions assist researchers investigating properties make development.

Language: Английский

---