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Genetic Counseling in Assisted Reproductive Technology
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Mendelian inheritance refers to single-gene disorders, where mutation(s) in a single nuclear gene causes a genetic disorder (Nussbaum et al., 2004). Other modes of inheritance include mitochondrial, where mutation occurs on the mitochondrial genome, and multifactorial, where multiple genetic, environmental, and random factors combine to cause a disease. Autosomal dominant, autosomal recessive, and X-linked inheritance patterns will be described here because these are the class of diseases for which PGT-M can be offered.
Evidence for Genetic Predispositions for Criminogenic Behavior
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
It is important to remember that a very large number of genes are likely to be involved in just one trait, as most human traits are highly complex and are influenced by many genetic variants, unlike the simple Mendelian inheritance we discussed earlier. In late 2018, for example, 535 new genetic regions were discovered to be associated with high blood pressure, adding to the already known 210.2 Therefore, any trait will be influenced by myriad genes to varying extents. In this meta-analysis of twin studies, the levels of heritability were clustered within certain trait types, but the average over the almost 18 000 traits was a heritability of 49%, with 69% of these due to additive genetic variation. The overall data did not suggest a strong influence of shared environment or non-additive genetic variation (that is, gene interaction).1
Mapping and sequencing: From gene to genome
Published in Peter S. Harper, The Evolution of Medical Genetics, 2019
Early human gene mapping was surrounded by a series of difficulties that did not bother those working with experimental species, such as Drosophila, which could be bred as wished and where large numbers reduced the need for complex statistics, but it did have one considerable advantage: already by 1950 there was an abundance of well- documented family data on rare inherited disorders, much of it brought together in Julia Bell's monumental Treasury of Human Inheritance, as described in Chapter 1. But the chance of a single family having two such disorders was minimal, so the problem initially was to find variable ‘marker loci’ following clear mendelian inheritance which could be tested against the segregation of a mendelian disorder or against other markers.
Incomplete penetrance of autosomal recessive anophthalmia in a large consanguineous family
Published in Ophthalmic Genetics, 2021
Masoud Dehghan Tezerjani, Behdokht Fathi Dizaji, Zahra Metanat, Mohammad Yahya Vahidi Mehrjardi
Anophthalmia (absence of eyes) and microphthalmia (small eyes) or A/M represents severe congenital defects of eye development. A/M can be uni- or bilateral and is prevalent at 3:100,000 to 30:100,000 (1). Both environmental and genetic factors contribute to A/M. However, genetic mutations are the predominant etiology including chromosomal abnormalities and mutations in over 100 genes with all patterns of Mendelian inheritance. In addition, variable expressivity between and within families has been reported. Mutations in most genes have shown full penetrance, but incomplete penetrance has been described in few genes (2). Numerous mutations in the aldehyde dehydrogenase 1 family member A3 (ALDH1A3) on chromosome 15q26.3 have been identified, which are believed to be responsible for approximately 10% of autosomal recessive A/M in consanguineous families of different ethnicities (3). This gene encodes an aldehyde dehydrogenase enzyme that biosynthesizes retinoic acid. The retinoic acid gradient along with the dorsoventral axis is essential for eye development (4). Genetic analysis of three Iranian patients suffering from non-syndromic bilateral anophthalmia using genome-wide SNP genotyping and autozygosity mapping revealed a novel homozygous missense mutation c.709 G>A in exon 7 of ALDH1A3 gene causing p.Gly237Arg substitution (5). Nevertheless, here we report a non-penetrance case who is a relative of our studied family with the same homozygous mutation in the ALDH1A3 gene without ocular involvement.
UK guidelines for the medical and laboratory procurement and use of sperm, oocyte and embryo donors (2019)
Published in Human Fertility, 2021
Helen Clarke, Shona Harrison, Marta Jansa Perez, Jackson Kirkman-Brown
Enquiries should also be made to establish that the potential donor’s genetic parents, siblings and offspring are free of:any of the major malformations outlined in the first bullet point above.non-trivial disorders showing Mendelian inheritance in the following categories:autosomal dominant or X-linked disorders, such as Huntington’s disease.autosomal recessive disease, particularly if it has a high frequency in the population e.g. cystic fibrosis.a chromosomal abnormality (unless the donor has a normal karyotype).a history of any mitochondrial disorders (oocyte and embryo donors only).
Clinical genomics and contextualizing genome variation in the diagnostic laboratory
Published in Expert Review of Molecular Diagnostics, 2020
James R. Lupski, Pengfei Liu, Pawel Stankiewicz, Claudia M. B. Carvalho, Jennifer E. Posey
Clinical genomics may perhaps best be defined, from a retrospective historical and operational standpoint [1,2], as utilizing the variation inherent to the personal genome of an individual patient to formulate a molecular diagnosis that may be potentially clinically impactful. A molecular diagnosis is not a clinical diagnosis, but rather variation of a gene or genome that may potentially have contributory consequences for the patient’s disease process, either at present, or in the future. The predictive advantage of molecular diagnoses is particularly poignant in cases for which there is no family history of the clinical diagnosis or clinically observed phenotype to otherwise impart clinical suspicion. Like other clinical laboratory testing, the derived molecular diagnosis needs to be contextualized with the clinical observations. When the molecular and the clinical diagnoses are consistent with the patient’s assessment, i.e. clinical history and physical examination, and the emerging clinical picture for a given gene or variant allele matches the clinical synopsis of an online Mendelian Inheritance in Man (OMIM: https://www.omim.org/) defined phenotype, it may be clinically informative. Molecular diagnosis can sometimes help resolve clinical diagnostic ambiguities and be used to explore a differential diagnosis for a known rare disease [3], but should we begin to utilize it to assist in the formulation of a differential diagnosis? Moreover, how can we further elevate the individual clinical case ‘solved rate’ for molecular diagnoses achieved through genomics?