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Journal of Medical Genetics Aug 1976Because syndrome designations permit the collection of data, they are much more than just lables. As new syndromes become delineated, their names connote (1) their...
Because syndrome designations permit the collection of data, they are much more than just lables. As new syndromes become delineated, their names connote (1) their phenotypic spectra, (2) their natural histories, and (3) their modes of inheritance or risk of recurrence. Various methods for designating new syndromes are reviewed, including naming them after (1) the basic defect, (2) an eponym, (3) one or more striking features, (4) an acronym, (5) a numeral, (6) a geographic term, and (7) some combination of the above. None of these systems of nomenclature is without fault. The advantages and disadvantages of each are discussed.
Topics: Disease; Eponyms; Female; Genetic Diseases, Inborn; Humans; Male; Phenotype; Syndrome; Terminology as Topic
PubMed: 957375
DOI: 10.1136/jmg.13.4.266 -
American Journal of Medical Genetics.... May 2023CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital...
CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.
Topics: Humans; Male; Female; Cryptorchidism; Phenotype; CHARGE Syndrome; Disorders of Sex Development; Genitalia; DNA Helicases; DNA-Binding Proteins
PubMed: 36794641
DOI: 10.1002/ajmg.a.63148 -
Journal of Medical Genetics Aug 2005In total, 200 families were reviewed with directly transmitted, cytogenetically visible unbalanced chromosome abnormalities (UBCAs) or euchromatic variants (EVs). Both... (Review)
Review
In total, 200 families were reviewed with directly transmitted, cytogenetically visible unbalanced chromosome abnormalities (UBCAs) or euchromatic variants (EVs). Both the 130 UBCA and 70 EV families were divided into three groups depending on the presence or absence of an abnormal phenotype in parents and offspring. No detectable phenotypic effect was evident in 23/130 (18%) UBCA families ascertained mostly through prenatal diagnosis (group 1). In 30/130 (23%) families, the affected proband had the same UBCA as other phenotypically normal family members (group 2). In the remaining 77/130 (59%) families, UBCAs had consistently mild consequences (group 3). In the 70 families with established EVs of 8p23.1, 9p12, 9q12, 15q11.2, and 16p11.2, no phenotypic effect was apparent in 38/70 (54%). The same EV was found in affected probands and phenotypically normal family members in 30/70 families (43%) (group 2), and an EV co-segregated with mild phenotypic anomalies in only 2/70 (3%) families (group 3). Recent evidence indicates that EVs involve copy number variation of common paralogous gene and pseudogene sequences that are polymorphic in the normal population and only become visible at the cytogenetic level when copy number is high. The average size of the deletions and duplications in all three groups of UBCAs was close to 10 Mb, and these UBCAs and EVs form the "Chromosome Anomaly Collection" at http://www.ngrl.org.uk/Wessex/collection. The continuum of severity associated with UBCAs and the variability of the genome at the sub-cytogenetic level make further close collaboration between medical and laboratory staff essential to distinguish clinically silent variation from pathogenic rearrangement.
Topics: Chromosome Aberrations; Euchromatin; Female; Humans; Inheritance Patterns; Male; Phenotype
PubMed: 16061560
DOI: 10.1136/jmg.2004.026955 -
Journal of Biomedical Semantics 2016Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput... (Review)
Review
Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput phenotyping program whose goal is to collect phenotype data for a knockout mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation.
Topics: Animals; Body Size; Female; Gene Ontology; Genotype; Male; Mice; Models, Animal; Phenotype; Reference Standards
PubMed: 26865945
DOI: 10.1186/s13326-016-0050-8 -
Mammalian Genome : Official Journal of... May 2006What causes phenotypic variation? By now it is clear that phenotype is a result of the interaction between genotype and environment, in addition to variation not readily... (Review)
Review
What causes phenotypic variation? By now it is clear that phenotype is a result of the interaction between genotype and environment, in addition to variation not readily attributable to either. Epigenetic phenomena associated with phenotypic variation at the biochemical, cellular, tissue, and organism level are now well recognized and are likely to contribute to the "intangible variation" alluded to. While it is clear that epigenetic modifications are mitotically heritable, the fidelity of this process is not well understood. Inheritance through more than one generation of meioses is even less well studied. So it remains unclear to what extent epigenetic changes contribute to phenotypic variation in natural populations. How might such evidence be obtained? What are the features of phenotypes that might suggest an epigenetic component? How much of the epigenetic component is truly independent of genetic changes? The answers to such questions must come from studies designed specifically to detect subtle, stochastically determined phenotypic variation in suitable animal models.
Topics: Adaptor Proteins, Signal Transducing; Animals; Carrier Proteins; DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Female; Genetic Variation; Genomics; Humans; Male; MutL Protein Homolog 1; Nuclear Proteins; Phenotype
PubMed: 16688527
DOI: 10.1007/s00335-005-0180-2 -
Nature Genetics Mar 2024Available genetically defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Here, we describe a...
Available genetically defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Here, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant bladder and prostate cancer models. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.
Topics: Male; Humans; Genotype; Phenotype; Neoplasms; Genetic Association Studies
PubMed: 38424461
DOI: 10.1038/s41588-024-01674-1 -
PLoS Genetics Apr 2017Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an...
Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an upper bound for the utility of genetic risk prediction models. Recent technological and statistical advances have enabled the estimation of additive heritability attributable to common genetic variants (SNP heritability) across a broad phenotypic spectrum. Here, we present a computationally and memory efficient heritability estimation method that can handle large sample sizes, and report the SNP heritability for 551 complex traits derived from the interim data release (152,736 subjects) of the large-scale, population-based UK Biobank, comprising both quantitative phenotypes and disease codes. We demonstrate that common genetic variation contributes to a broad array of quantitative traits and human diseases in the UK population, and identify phenotypes whose heritability is moderated by age (e.g., a majority of physical measures including height and body mass index), sex (e.g., blood pressure related traits) and socioeconomic status (education). Our study represents the first comprehensive phenome-wide heritability analysis in the UK Biobank, and underscores the importance of considering population characteristics in interpreting heritability.
Topics: Adult; Aged; Biological Specimen Banks; Blood Pressure; Female; Gene-Environment Interaction; Genetic Diseases, Inborn; Genome-Wide Association Study; Humans; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Sex Characteristics; Social Class; United Kingdom
PubMed: 28388634
DOI: 10.1371/journal.pgen.1006711 -
Biology Letters Oct 2016Pigmentation is a classic phenotype that varies widely and adaptively in nature both within and among taxa. Genes underlying pigmentation phenotype are highly...
Pigmentation is a classic phenotype that varies widely and adaptively in nature both within and among taxa. Genes underlying pigmentation phenotype are highly pleiotropic, creating the potential for functional trade-offs. However, the basic tenets of this trade-off hypothesis with respect to life-history traits have not been directly addressed. In natural populations of Drosophila melanogaster, the degree of melanin pigmentation covaries with fecundity and several other fitness traits. To examine correlations and potential trade-offs associated with variation in pigmentation, we selected replicate outbred populations for extreme pigmentation phenotypes. Replicate populations responded rapidly to the selection regime and after 100 generations of artificial selection were phenotyped for pigmentation as well as the two basic fitness parameters of fecundity and longevity. Our data demonstrate that selection on pigmentation resulted in a significant shift in both fecundity and longevity profiles. Selection for dark pigmentation resulted in greater fecundity and no pronounced change in longevity, whereas selection for light pigmentation decreased longevity but did not affect fecundity. Our results indicate the pleiotropic nature of alleles underlying pigmentation phenotype and elucidate possible trade-offs between pigmentation and fitness traits that may shape patterns of phenotypic variation in natural populations.
Topics: Animals; Drosophila melanogaster; Female; Fertility; Longevity; Male; Phenotype; Pigmentation; Selection, Genetic
PubMed: 28120808
DOI: 10.1098/rsbl.2016.0625 -
Evolution; International Journal of... Sep 2022Sex-specific dominance reversals (SSDRs) in fitness-related traits, where heterozygotes' phenotypes resemble those of alternative homozygotes in females versus males,...
Sex-specific dominance reversals (SSDRs) in fitness-related traits, where heterozygotes' phenotypes resemble those of alternative homozygotes in females versus males, can simultaneously maintain genetic variation in fitness and resolve sexual conflict and thereby shape key evolutionary outcomes. However, the full implications of SSDRs will depend on how they arise and the resulting potential for evolutionary, ecological and environmental modulation. Recent field and laboratory studies have demonstrated SSDRs in threshold(-like) traits with dichotomous or competitive phenotypic outcomes, implying that such traits could promote the emergence of SSDRs. However, such possibilities have not been explicitly examined. I show how phenotypic SSDRs can readily emerge in threshold traits given genetic architectures involving large-effect loci alongside sexual dimorphism in the mean and variance in polygenic liability. I also show how multilocus SSDRs can arise in line-cross experiments, especially given competitive reproductive systems that generate nonlinear fitness outcomes. SSDRs can consequently emerge in threshold(-like) traits as functions of sexual antagonism, sexual dimorphism and reproductive systems, even with purely additive underlying genetic effects. Accordingly, I identify theoretical and empirical advances that are now required to discern the basis and occurrence of SSDRs in nature, probe forms of (co-)evolutionary, ecological and environmental modulation, and evaluate net impacts on sexual conflict.
Topics: Animals; Biological Evolution; Female; Male; Phenotype; Selection, Genetic; Sex; Sex Characteristics
PubMed: 35803581
DOI: 10.1111/evo.14563 -
Poultry Science Dec 2021Low fertilization rate is the main reason to limit the development of artificial insemination (AI) technology in ducks. However, the libido of male livestock has been...
Low fertilization rate is the main reason to limit the development of artificial insemination (AI) technology in ducks. However, the libido of male livestock has been confirmed to be related to semen quality and fertilization rate, and we found that the libido of drakes was different. Thus, the research on the libido of drakes may be the key to further develop and apply AI technology. In this research, we established the first scoring standard for libido evaluation in drakes based on the performance of drakes during training period. Phenotypically, the body weight of high libido group was lighter than that of the other groups, while the weight of testis and epididymis in the high libido group was higher than that in the low libido group. Furthermore, we constructed the first expression profile of hypothalamus, pituitary, testis, and epididymis of drakes with high or low libido. There were 2, 1822, 214, and 892 differentially expressed genes (DEGs) in hypothalamus, pituitary, testis, and epididymis. The expression and sequence of Translocation Associated Membrane Protein 2 (TRAM2) were different in high and low libido drakes, indicating that it may be a candidate gene related to drake's libido. The estrogen, prolactin, and oxytocin signaling pathways were all activated in the pituitary of the low libido group. Meanwhile, the metabolic and oxidative phosphorylation pathways were enriched by DEGs in pituitary, testis and epididymis. Our research reveals that the difference in metabolic may cause changes in body weight of drakes, resulting in altered hormone levels and oxidative phosphorylation of gonad, which negatively affects libido and spermatogenesis in drakes. These results provide novel insights into the avian libido and will help better understand the underlying molecular mechanisms.
Topics: Animals; Chickens; Libido; Male; Phenotype; Semen Analysis; Testis
PubMed: 34700098
DOI: 10.1016/j.psj.2021.101503