China
Africa
Explore chapters and articles related to this topic
Neurological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Some patients with single gene autosomal dominant conditions will give a clear family history. Many other conditions have polygenic inheritance, but this is rarely helpful diagnostically. Importantly, a family history of, for instance, aneurysmal SAH or Huntington's disease (HD) may be a major source of worry, even if the clinical features would not support such a diagnosis.
Basic genetics and patterns of inheritance
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
In multifactorial inheritance, it is postulated that genetic influences from both parents, in combination with environmental factors, lead to a specific birth defect or disorder. In polygenic inheritance, multiple genetic influences in combination act together to produce a disorder. Examples of birth defects with multifactorial inheritance include isolated congenital heart defects, cleft lip with or without cleft palate, cleft palate, neural tube defects, pyloric stenosis, and congenital dislocation of the hips (Table 4). In multifactorial disorders, there is no evidence to suggest simple Mendelian inheritance. For example, the defect does not necessarily appear in sequential generations of a family, as would an autosomal dominant condition due to a single-gene mutation. However, there may be clustering of the defect in more than one member of a pedigree. The appearance of multifactorial disorders has been explained by a threshold model in which certain genes present in an individual, along with prenatal environmental factors, accumulate toward a threshold. If an individual has enough of these genes and factors, a threshold will be crossed and the defect will appear (32).
The cardiovascular system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Mary N Sheppard, C. Simon Herrington
A polygenic inheritance has been established. The candidate genes include those encoding angiotensinogen, which is estimated to account for 6% of blood pressure variation in humans, renin, and atrial natriuretic peptide receptor genes.
Management of congenitally corrected transposition from fetal diagnosis to adulthood
Published in Expert Review of Cardiovascular Therapy, 2023
ccTGA is a rare congenital heart disease (CHD) and accounts for approximately 0.03% of all CHDs. The annual incidence of ccTGA has been reported to be around 1/25,500 live births [8]. The etiology of the defect is not known. Recent studies indicate a relationship between the development of ccTGA and dysfunction of cilia. In a large multicenter study of 1043 unrelated ccTGA probands, an association between ccTGA, d-TGA, laterality defects, and in some cases primary ciliary dyskinesia was shown [9]. Another study revealed a high prevalence of an abnormal ciliary function in isolated ccTGA patients independent of laterality abnormalities [10]. Finally, mutations of genes involved in ciliogenesis and cilia-transduced signaling pathways in a ccTGA exome sequencing study have been described. An oligogenic or polygenic inheritance of the disease is suggested [11].
Human height: a model common complex trait
Published in Annals of Human Biology, 2023
Mitchell Conery, Struan F. A. Grant
In summary, height is broadly similar to other complex phenotypes apart from its ease of measurement and high heritability. These factors have made it a widely employed model trait for studying the topic of complex phenotype inheritance. However, throughout the GWAS era, height has not always been at the leading edge of variant and gene discovery, that is until its most recent GWAS by Yengo et al. In having at last closed the gap of missing common SNP-based heritability for a common trait, Yengo et al. may have signalled the beginning of the end of the GWAS era. Their work demonstrates the limits to endlessly increasing GWAS sample sizes and highlights the need for greater diversity in study populations. Moreover, their results directly contradict the most extreme form of the omnigenic model and imply that highly polygenic inheritance is likely a more appropriate model for complex traits. The analysed polygenic score results also suggest that when sample sizes across complex phenotype GWAS efforts increase to the point of heritability saturation across all ancestries, polygenic risk scores will become powerful tools for the prediction of disease risk. However, the implications of this study for the identification of individual effector disease genes are less optimistic. Should the GWAS era be drawing to a close, the era of gene identification that follows will surely be one of both great challenges and opportunities.
Increase in DNA methylation in patients with amyotrophic lateral sclerosis carriers of not fully penetrant SOD1 mutations
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2018
Fabio Coppedè, Andrea Stoccoro, Lorena Mosca, Roberta Gallo, Claudia Tarlarini, Christian Lunetta, Alessandro Marocchi, Lucia Migliore, Silvana Penco
ALS is mainly sporadic (SALS), and only 5–10% of the cases are inherited (familial ALS = FALS). Four major genes account for most of FALS and for a small percentage of the sporadic cases, namely SOD1 (accounting for 12% of FALS and about 1% of SALS cases), TARDBP (5% of FALS and less than 1% of SALS), FUS (4% of FALS and less than 1% of SALS) and C9orf72 (40% of FALS and about 7% of SALS). A few other genes play a significant role in inherited ALS forms, each accounting for less than 1% of the cases (2,3). In addition to these highly penetrant genes, genome-wide screening has identified more than 100 low penetrance ALS loci, suggesting a polygenic inheritance model and a strong contribution of environmental factors in SALS (2,3). Risk of ALS may be modulated by environmental factors, gender and aging, which could be linked to epigenetic events, i.e. changes in gene expression not resulting from changes in the DNA sequence (4,5). In this regard, increasing evidence suggests that epigenetic modifications such as DNA methylation and histone tail modifications might contribute to ALS pathogenesis, and global changes in DNA methylation have been reported in blood and spinal cord DNA of ALS patients, as well as in monozygotic twins discordant for the disease, often leading to altered expression of dozens of genes (6–8).