Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inheritance Patterns”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed2005

Oocyte-expressed genes affecting ovulation rate.

From examination of inherited patterns of ovulation rate in sheep, several breeds have been identified with point mutations in two growth factor genes (BMP15 and GDF9) and a related receptor (ALK6) that are expressed in oocytes. Five different point mutations have been identified in the BMP15 gene, one in GDF9 and one in ALK6. Animals heterozygous for these mutations or heterozygous for two of these mutations or homozygous for the ALK6 mutation have higher ovulation rates (i.e. +0.6-10) than their wild-type contemporaries. Animals homozygous for the BMP15 or GDF9 mutations are sterile due to arrested follicular development from the primary stage of growth. The BMP15 and GDF9 mutations are thought to result in reduced levels of mature protein or altered binding to cell-surface receptors. In sheep, GDF9 mRNA is present in germ cells before and after ovarian follicular formation as well as throughout follicular growth, whereas BMP15 mRNA is found in oocytes only from the primary stage of growth. Also ALK6 together with related cell-surface receptors such as ALK5 and BMPRII mRNA are present in oocytes at most, if not all, stages of follicular growth. Both GDF9 and BMP15 proteins are present in follicular fluid indicating that they are secreted products. Immunisation of sheep with GDF9 or BMP15 peptides shows that both growth factors are essential for follicular development, ovulation and/or corpus luteum formation. In animals with the ALK6 mutation, ovarian follicles undergo precocious maturation leading to three to seven follicles ovulating at smaller diameters without any increase above wild-types in the ovarian secretions of steroid or inhibin. One important consequence of the ALK6 mutation appears to be a decreased ability of some BMPs to inhibit differentiation of follicular cells. Current findings in sheep suggest that BMP15, GDF9 and ALK6 are targets for new methods of fertility regulation in some mammals.

Animals↗
PubMed2005

The significance of mitochondria for embryo development in cloned farm animals.

The role of mitochondria in remodeling of the donor cell nucleus in cloned animals has gained increased attention, as mitochondria interact in direct or indirect ways with the donor cell nuclear DNA. Mitochondria comprise 1% of the genetic material that is contributed to the developing embryo by the recipient oocyte and provide the energy that is required for embryo development. In this review we compare mitochondria distribution in various species and the importance of mitochondria distribution for embryo development. We also compare the inheritance pattern of mitochondria in cloned embryos that remains unresolved, as the donor cell nucleus is typically transferred with surrounding cytoplasm including mitochondria which become destroyed in some but not all species. We review the role of mitochondria in cloned farm animals with emphasis on nucleo-cytoplasmic interactions and consequences for embryo development.

Animals↗
PubMed2005

The general public's information needs and perceptions regarding hereditary cancer: an application of the Integrated Change Model.

The Integrated Change Model (the I-Change Model) was used to analyse the general public's need and perceptions concerning receiving information on the role of hereditary factors with regard to cancer. The results from a study in 457 Dutch adults showed that 25% correctly indicated the types of cancer where hereditary factors can play a role. Respondents, however, overestimated the role of hereditary factors causing breast cancer. Recognition of warning signs was low, as was the recognition of inheritance patterns. Participants wanted to know the types of cancer with hereditary aspects, how to recognise hereditary cancer in the family, personal risks and the steps to be taken when hereditary predisposition is suspected. The most popular information channels mentioned were leaflets, the general practitioner, and the Internet. Respondents interested in receiving information on heredity and cancer were more often female, had had experiences with hereditary diseases, had more knowledge, perceived more advantages, encountered more social support in seeking information, and had higher levels of self-efficacy. Education should outline the most important facts about hereditary cancer, how to get support, and create realistic expectations of the impact of genetic factors.

Adolescent↗
PubMed2004

Familial retinal migraines.

Approximately 25% of sufferers of retinal migraine are thought to have a positive family history. Retinal migraines can cause both transient, and rarely permanent, unilateral monocular visual loss. This report of familial retinal migraines furthers our understanding of this particular migraine subtype. Two families with retinal migraines are reported suggesting an autosomal-dominant inheritance pattern with variable expression and penetrance.

Adolescent↗
PubMed2004

What was classical genetics?

I present an account of classical genetics to challenge theory-biased approaches in the philosophy of science. Philosophers typically assume that scientific knowledge is ultimately structured by explanatory reasoning and that research programs in well-established sciences are organized around efforts to fill out a central theory and extend its explanatory range. In the case of classical genetics, philosophers assume that the knowledge was structured by T. H. Morgan's theory of transmission and that research throughout the later 1920s, 30s, and 40s was organized around efforts to further validate, develop, and extend this theory, I show that classical genetics was structured by an integration of explanatory reasoning (associated with the transmission theory) and investigative strategies (such as the 'genetic approach'). The investigative strategies, which have been overlooked in historical and philosophical accounts, were as important as the so-called laws of Mendelian genetics. By the later 1920s, geneticists of the Morgan school were no longer organizing research around the goal of explaining inheritance patterns; rather, they were using genetics to investigate a range of biological phenomena that extended well beyond the explanatory domain of transmission theories. Theory-biased approaches in history and philosophy of science fail to reveal the overall structure of scientific knowledge and obscure the way it functions.

Genetics↗
PubMedDate not supplied

Unexplained visual loss.

Dominant optic atrophy is the most common heredodegenerative optic neuropathy. Typically, patients present with slowly progressive, bilaterally decreased central visual acuity. Subtle central or cecocentral visual field defect and normal peripheral isopters are demonstrated with perimetry. A defect in blue-yellow discrimination (tritan error axis) is the most common type of dyschromatopsia, however protan and deutan axes may be superimposed. A characteristic optic disk appearance includes temporal disk pallor with excavation. An autosomal dominant inheritance pattern can often be elicited from the family history.

Adult↗
PubMed2004

Genetic analysis of syndactyly in German Holstein cattle.

Congenital syndactyly with a variable number of affected feet was observed in eight black and white German Holstein calves. Analysis of the pedigree data revealed that all affected individuals could be traced back to a single founder. The pedigree was consistent with monogenic autosomal recessive inheritance and variable expressivity. Bovine syndactyly or "mulefoot" has been previously shown to map on the telomeric end of bovine chromosome 15 and we performed PCR genotyping of microsatellite markers spanning 27 cM of this chromosomal region to test the new cases for genetic linkage with the phenotype. The haplotype segregation confirmed the suggested inheritance pattern of the mulefoot mutation in this family and markers RM004, BM848 and BMS820 showed significant linkage to the phenotype. The results confirmed the chromosomal location of the mulefoot gene in this pedigree. Furthermore the study demonstrated that although marker testing has been available for nearly a decade the use of mulefoot carriers in cattle breeding remains uncontrolled. The presented family provides a resource for positional cloning of the causative mutation.

Animals↗
PubMedDate not supplied

Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse.

To better understand carnitine palmitoyltransferase 1a (liver isoform, gene=Cpt-1a, protein=CPT-1a) deficiency in human disease, we developed a gene knockout mouse model. We used a replacement gene targeting strategy in ES cells that resulted in the deletion of exons 11-18, thus producing a null allele. Homozygous deficient mice (CPT-1a -/-) were not viable. There were no CPT-1a -/- pups, embryos or fetuses detected from day 10 of gestation to term. FISH analysis demonstrated targeting vector recombination at the expected single locus on chromosome 19. The inheritance pattern from heterozygous matings was skewed in both C57BL/6NTac, 129S6/SvEvTac (B6;129 mixed) and 129S6/SvEvTac (129 coisogenic) genetic backgrounds biased toward CPT-1a +/- mice (>80%). There was no sex preference with regard to germ-line transmission of the mutant allele. CPT-1a +/- mice had decreased Cpt-1a mRNA expression in liver, heart, brain, testis, kidney, and white fat. This resulted in 54.7% CPT-1 activity in liver from CPT-1a +/- males but no significant difference in females as compared to CPT-1a +/+ controls. CPT-1a +/- mice showed no fatty change in liver and were cold tolerant. Fasting free fatty acid concentrations were significantly elevated, while blood glucose concentrations were significantly lower in 6-week-old CPT-1a +/- mice compared to controls. Although the homozygous mutants were not viable, we did find some aspects of haploinsufficiency in the CPT-1a +/- mutants, which will make them an important mouse model for studying the role of CPT-1a in human disease.

Animals↗
PubMed2002

[Incidence of A1555G mutations in the mitochondrial DNA and 35delG in the GJB2 gene (connexin-26) in families with late onset non-syndromic sensorineural hearing loss from Cantabria].

INTRODUCTION: Sensorineural deafness is a very common disorder in humans, which affects approximately 10% of the population. Genetic causes are suggested to be responsible for more than half of the cases. The A1555G mutation in the mitochondrial 12S rRNA gene and the 35delG mutation in the GJB2 gene are the most common mutations for sensorineural deafness in the Spanish population. METHODS: A genetic study was carried out in order to determine the frequency of the mutations A1555G in the mitochondrial DNA and 35delG in the connexin-26 gene in 21 patients from 21 non-consanguineous unrelated families affected by late-onset bilateral non-syndromic sensorineural hearing loss from Cantabria. RESULTS: The A1555G mutation was found in 6 patients. Five of these 6 patients had been treated with aminoglycosides. In all of them the auditory impairment affected mainly the high frequencies. The 35delG mutation was not found in any of the patients. CONCLUSIONS: The A1555G mutation in the mitochondrial DNA has been found to be the most common amongst the Cantabrian population. The A1555G mutation should be suspected in those members of families affected by sensorineural hearing impairment with a maternal inheritance pattern and ototoxicity from treatment with aminoglycoside antibiotics. The 35delG mutation in the GJB2 gene does not seem to be a major cause of deafness in families with late-onset non-syndromic sensorineural hearing loss in our area.

Adolescent↗
PubMed1994

Genetic clues to glaucoma's secrets. The L Edward Jackson Memorial Lecture. Part 2.

Major advances in the medical and surgical treatment of glaucoma have occurred since the first Edward Jackson Memorial lecture was delivered 50 years ago. Collaborative clinical trials under the sponsorship of the National Eye Institute are adding to our knowledge about which patients to treat and how to treat them. Despite these clinical advances, an understanding of the pathophysiologic and biochemical mechanisms that cause the disease remain unknown. The 40th anniversary of the discovery of the DNA double helix provides a springboard for a historical perspective on the heritability of glaucoma. A large pedigree is presented of a family with autosomal dominantly inherited primary open-angle glaucoma of juvenile onset. This is the second family with this clinical entity to show genetic linkage to the long arm of chromosome 1. Other forms of primary open-angle glaucoma with adult onset are presented wherein the inheritance pattern suggests autosomal recessive transmission. Thus far, linkage analysis does not suggest a genetic relationship to the autosomal dominant juvenile-onset pedigree that links to the long arm of chromosome 1. It is hoped that an emphasis on clinical and molecular genetic studies of glaucoma will yield protein defects that can be targeted for treatment. It is emphasized that the clinical ophthalmologist can participate in this important work by finding families with glaucoma and collaborating with individuals capable of extracting DNA, manipulating it, and performing genetic linkage and positional cloning studies.

Adult↗
PubMed1980

Atrophic maculopathy associated with hereditary ataxia.

Two siblings had atrophic maculopathy associated with hereditary ataxia clinically defined as an olivopontocerebellar degeneration. The macular changes were suggestive of an early bull's-eye maculopathy in one case and of a late atrophic stage of bull's-eye maculopathy in the other. This suggests that concentric annular (bull's-eye) macular dystrophy may occur as part of olivopontocerebellomacular degeneration. Exogenous causes were excluded. The inheritance pattern was autosomal recessive or irregular autosomal dominant. The relationship of these two degenerative disorders is not yet clear. This combination of findings has been, to our knowledge, only rarely described.

Adolescent↗
PubMed2003

Psoriasiform dermatitis susceptibility in Itgb2(tm1Bay) PL/J mice requires low-level CD18 expression and at least two additional loci for progression to severe disease.

Itgb2(tm1Bay) PL/J mice express low levels of the beta(2) integrins and, unlike Itgb2(tm1Bay) C57BL/6J mice, spontaneously develop psoriasiform dermatitis with several similarities to human psoriasis. To define the genetic requirements for skin disease susceptibility we analyzed more than 500 F2 progeny from an Itgb2(tm1Bay) (PL/J x C57BL/6J) intercross. We found that 23.5% developed chronic inflammatory skin disease, although significant differences in severity were observed. Another CD18 mutation, Itgb2(tm2Bay), has now been generated that completely eliminates CD18 expression. Surprisingly, of 10 Itgb2(tm2Bay) homozygote PL/J N4 mice generated, none showed clinical or histopathological evidence of disease. However, Itgb2(tm1Bay)/Itgb2(tm2Bay) PL/J mice developed dermatitis indistinguishable from Itgb2(tm1Bay) PL/J mice. In addition, approximately half of Itgb2(tm1Bay)/Itgb2(tm2Bay) (C57BL/6J x PL/J)F1 mice were found to develop mild psoriasiform dermatitis identical to the early stages of disease seen in Itgb2(tm1Bay) PL/J mice. Collectively, these results suggest a complex inheritance pattern of psoriasiform dermatitis in this model that involves lowered, but not absent, CD18 expression and at least two additional PL/J loci for the development of severe disease. The susceptibility allele can act in either a heterozygous or homozygous state, dependent on the level of CD18 expression.

Animals↗
PubMedDate not supplied

Genetic heterogeneity of autosomal dominant amelogenesis imperfecta demonstrated by its exclusion from the AIH2 region on human chromosome 4Q.

Amelogenesis imperfecta (AI) is a group of hereditary enamel defects, characterized by large clinical diversity. On the basis of differences in clinical manifestation and inheritance pattern, 14 different subtypes have been recognized. A locus for autosomal dominant AI (ADAI) of local hypoplastic type was recently mapped to the region between D4S392 and D4S395 on the long arm of chromosome 4. To test whether the chromosome 4 locus is responsible for other forms of AI as well, a linkage study was carried out with 17 families representing at least five clinical forms of ADAI. Admixture tests for heterogeneity performed with the marker D4S2456 gave statistical support for genetic heterogeneity of ADAI with the odds 78:1. Linkage to the ADAI locus on chromosome 4q (AIH2) could only be demonstrated with families expressing the local hypoplastic type, and there was no support for heterogeneity within that group of families. Furthermore, linkage could be excluded for five families with other clinical forms of ADAI. The data therefore demonstrated that ADAI is genetically heterogeneous, and that at least two loci for it exist.

Amelogenesis Imperfecta↗
PubMed2001

The role of perinatal stress in simplex retinitis pigmentosa: evidence from surveys in Australia and the United States.

BACKGROUND: In experimental models of several forms of human retinitis pigmentosa (RP) the dystrophy begins in the neonatal period, during a "critical period" in which photoreceptors are sensitive to hypoxia. We performed a study to test whether perinatal stress is associated with human RP, particularly in simplex (nonfamilial) cases. METHODS: Two surveys were carried out in 1999. In one, Australians with RP were surveyed for information on whether they had experienced stress at birth and whether any members of their family had RP. In the other, the diagnostic type and inheritance patterns of a group of patients with RP seen at a university-affiliated eye institute in Los Angeles between 1997 and 1999 were established as part of their clinical assessment. In neither cohort was the RP part of a syndrome. RESULTS: After entry criteria were applied, there were 293 cases (of a total of 446 replies) available for analysis from the Australian survey and 119 cases (after exclusion of 229 cases with incomplete data) from the US survey. A total of 52.2% and 53.8% of the cases respectively were simplex. Perinatal stress was reported by about 15% of the respondents with familial RP (15.0% in the Australian cohort and 14.5% in the US cohort), compared with 30% of those with simplex RP (27.4% and 29.7% respectively), a significant difference (p < 0.05). In the Australian cohort four forms of stress--cyanosis, difficult presentation, prematurity and a perinatal period of intensive care--were reported more than twice as often by respondents in the simplex group than those in the familial group. For only one factor, cyanosis, was the difference between the two groups significant (chi2 test, p = 0.01). In the US cohort no single form of stress was significantly related to simplex RP. INTERPRETATION: Our findings support the hypothesis that perinatal stress is associated with simplex RP in a minority of cases. Larger cohorts need to be studied to test whether perinatal stress can interact with predisposing genes in the genesis of some forms of RP.

Australia↗
PubMed1980

Autosomal recessive hereditary congenital aplasia of the vasa deferentia in four siblings.

Congential absence of the vas deferens is a frequently occurring cause of infertility. Such a disorder can be accompanied by renal agenesis and therefore pyelography should be performed. That such a disorder in man could have genetic aspects has not been mentioned in the literature, but there are reports that this disorder is hereditary in some animals. A family of nine children is described in which four of the five sons were infertile as a result of congenital aplasia of the vasa deferentia. Since there was no evidence that these men had cystic fibrosis and since they did not have the mosaic form of Klinefelter's syndrome, an unrelated developmental defect is postulated. The genetic aspects are discussed and the conclusion is made that the inheritance pattern most probably is autosomal recessive. Finally, the therapeutic problems are discussed. At this time, surgical treatment of this disorder is not encouraging.

Adult↗
PubMed1997

A juvenile polyposis tumor suppressor locus at 10q22 is deleted from nonepithelial cells in the lamina propria.

BACKGROUND & AIMS: Juvenile polyps are characterized by an abundant lamina propria that lacks smooth muscle and may contain cystically dilated glands, with epithelium that seems normal and is nondysplastic. Rarely, an autosomal dominant inheritance pattern occurs. The aim of this study was to test the hypothesis that the genetic defect in both sporadic juvenile polyps and hereditary juvenile polyposis involves loss of function for a tumor suppressor gene. METHODS: Allelic losses were detected by comparing normal DNA with tumor DNA from a series of 47 juvenile polyps from 16 patients using polymerase chain reaction amplification of microsatellite markers and fluorescent in situ hybridization (FISH). RESULTS: Somatic deletions at 10q22 were detected in 39 of 47 juvenile polyps (83%) from 16 unrelated patients with either hereditary or sporadic juvenile polyps, and the minimum overlap localized juvenile polyposis coli to the 3-cM interval D10S219-D10S1696. Fluorescent in situ hybridization shows that the cells affected by deletion mutation reside exclusively in the lamina propria, not in the epithelium. CONCLUSIONS: The location of a novel tumor suppressor gene on chromosome 10 that is affected by deletion mutation in the majority of juvenile polyps was mapped. Unlike adenomas and carcinomas of the colonic epithelium, juvenile polyps originate in the lamina propria.

Adolescent↗
PubMedDate not supplied

Genes and syndromic hearing loss.

UNLABELLED: Syndromes that are associated with hearing loss include Waardenburg, Stickler (STL), Jervell and Lange-Nielsen, Usher (USH), Alport, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, and sensorineural hearing loss (MELAS) and mitochondrial encephalomyopathy, myoclonus epilepsy, ragged-red fibers, and sensorineural hearing loss (MERRF). Waardenburg and STL show an autosomal dominant pattern of inheritance, while Jervell and Lange-Nielsen and USH are autosomal recessive, and Alport is usually X-linked. Mutations in specific genes that are associated with each of these syndromes have been identified, and genetic diagnostic tests are becoming available. The goal of ongoing research is to understand the functions of the proteins encoded by these genes, and develop effective therapies based on knowledge of the underlying causal mutations. LEARNING OUTCOMES: The reader will be introduced to basic genetic principles and will understand that (1) the etiology of hearing loss is usually genetic and many patients should be referred to a clinical geneticist; (2) a negative family history does not mean that the hearing loss is not genetic; (3) hearing loss may be part of a syndrome for which early detection and intervention for associated anomalies is necessary; and (4) many different mutations in a large number of genes underlie hearing loss.

DNA, Mitochondrial↗
PubMed1996

Characterization of a new hereditary thrombopathy in a closed colony of Wistar rats.

A new hereditary thrombopathy has been identified in a closed colony of Wistar rats. A simple and reproducible cuticle bleeding time test was developed as a rapid screening procedure for the bleeding diathesis. Affected animals exhibit markedly prolonged bleeding times and complete absence of platelet aggregation either with adenosine diphosphate (ADP) or with thrombin. Inheritance data suggest an autosomal dominant inheritance pattern with variable penetrance. Coagulation tests, platelet counts, plasma von Willebrand factor (vWF) activity, and clot retraction are within normal limits in thrombopathic animals. GPIb-dependent botrocetin-induced platelet agglutination was present in washed thrombopathic rat platelets. No discernible abnormality of intraplatelet organelles or granules was seen by transmission electron microscopy of thrombopathic platelets. A qualitative morphologic assessment of intraplatelet fibrinogen in thrombopathic rat platelets showed no discernible difference as compared with control rat platelets. Thrombopathic rat platelets exhibit decreased glycoprotein IIb/IIIa (GPIIb/IIIa) antigen by flow cytometric analysis and markedly decreased iodine 125-labeled fibrinogen binding to platelet GPIIb/IIIa after ADP activation. This rat colony demonstrates a unique thrombopathy, distinct from previously described animal thrombopathies, with some characteristics of variant Glanzmann's thrombasthenia. This animal model may provide further insight into the regulatory mechanisms and pathophysiology of platelet GPIIb/IIIa.

Animals↗