SEARCH · Search PubMed
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.
In testing a single dominant gene hypothesis we often are not able directly to measure the inherited trait. A typical situation is one where we only have one or more fallible indicators of the trait under study. The statistical method proposed requires that we have measurements on several such indicators for each of the parents of probands known to possess the trait.
A kindred of 68 French Acadians who were heterozygous for a dominant gene of Charcot-Marie-Tooth disease associated with peripheral nerve hypertrophy are described. Marriage between 2 heterozygotes resulted in 2 homozygous offspring. Clinical features of the homozygotes were similar to the classic description of Dejerine-Sottas disease. Laboratory studies in this family revealed no chemical, metabolic, or chromosomal abnormalities in either the homozygotes or the heterozygotes.
A unique pedigree is presented which shows tuberous sclerosis in three generations of a family, in which two heterozygotes for the mutant gene were found to be clinically asymptomatic. A genetic model is proposed to explain these findings based upon the segregation of a second unlinked autosomal dominant gene modifying the expression of the gene for tuberous sclerosis.
Among 75 members of a Danish family, 12 were found with a syndrome not previously described. Clinically, the syndrome consists of low body height and rigid flat feet, with weight-bearing pain in the feet. Radiologically, the deformation of the feet is a medial synostosis between the talus and the calcaneus combined with ankle joint dysplasia. The cause of the syndrome is most probably an autosomal dominant gene with complete penetrance. No linkage was found of the gene to 18 marker genes.
The beginning of synthesis, localization and content of crystallins were studied in the developing lenses of 9--13 and 15 days old embryos of CatFr/CatFr and +/+ mice by means of immunofluorescence and polyacrilamide gel electrophoresis. The mutant gene CatFr was shown not to affect the crystallin synthesis. Alpha-crystallins are first to be synthesized in the cytoplasm of cells of the proximal part of the lens vesicle (10 days of development). Gamma-crystallins are detected for the first time in the lens of 11 days old embryos in the cytoplasm of developing lens fibers which lost their ability to divide. The differences in the time of synthesis of alpha- and gamma-crystallins are, possibly, related to their different role in the process of lens fiber differentiation.
A woman with the autosomal dominant syndrome of preauricular pits, cervical fistulae, and partial deafness gave birth to two children with preauricular pits and severe renal dysgenesis. The facies had some features of the Potter facies of renal agenesis. One child died soon after birth because of pneumothorax and immature development of the lungs. We suggest that all infants with renal agenesis or dysgenesis be examined for preauricular pits because of the high recurrence risk of renal anomalies in families with this syndrome.
Explore the source record for details and available documents.
The secondary cytotoxic responses to the male specific antigen (H-Y) in in mice show H-2 restrictions so that cytotoxic female cells must share K and/or D end antigen with the male target cells. The production of cytotoxic cells is under the control of Ir genes, thus offering the possibility of studying the function of Ir genes in H-2-restricted cytotoxic responses. There are two kinds of Ir genes regulating this response; the dominant gene in the H-2b haplotype and complementary genes in other haplotypes. Now we have been able to map the dominant gene and some of the complementary genes: the dominant genes is in IAb, and in H-2k/H-2d complementation, the Ir genes are in ICk and ICd, and in H-2k/H2s and H-2k/H-2q complementations, at least the H-2k gene is in IC.
The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders.
Genetic effects of 5-thio-D-glucose (5-thio) were tested in male mice by the dominant lethal gene test. Males were treated with phosphate buffered saline (PBS) or 5-thio dissolved in PBS by oral intubation daily at 40 or 60 mg/kg for 7 or 35 successive days. Average implantations per pregnant female and the intrauterine postimplantation losses in females mated with 5-thio trated males did not show any significant differences when compared statistically with parallel controls. Furthermore, the compound had no effect on the appearance and mating behavior of the male mice. This is the first report on the genetic effects of 5-thio to show that the compound in the treatment regimens studied were not mutagenic in terms of the induction of dominant lethal mutation in male mice.
A large pedigree wherein members are predisposed to atrial septal defect (ASD) and associated cardiovascular anomalies has been studied. There were ten direct line relatives with ASD verified by cardiac catheterization and/or surgery and in one case by reliable medical history. The pedigree shows vertical transmission of ASD through four generations. Estimates of the genetic segregation ratio were near 50%, indicating that predisposition to ASD among family members was due to a deleterious autosomal dominant gene. Family members have also manifested other congenital heart anomalies, consistent with pleiotropic effects of the putative gene. Electrocardiograms in six ASD patients revealed an absence of prolonged P-R interval. In the light of prior studies showing prolonged P-R interval in familial ASD, we suggest the existence of at least two distinct hereditary varieties of ASD, one with and one without a prolonged P-R interval.
By radioimmunoassay (RIA) mammary tumour virus (MTV) antigens were detected in individual milk samples of C3Hf mice, (female BALB/c X male C3Hf)F1 mice and (female C3Hf X male BALB/c)F1 mice; milk samples of BALB/c mice were negative. In the segregating backcross I population, female BALB/c X male (female BALB/c X male C3Hf) viral antigens were found in the milk of 93 out of 169 mice (55%). In the Bc II population (daughters of Bc I mothers and BALB/c fathers) two groups were distinguished. In the first group, derived from positive Bc I mothers, 55 out of 110 mice (50%) had detectable levels of viral antigens in the milk. In the second group, progeny of negative Bc I mothers, 1 mouse out of 47 was positive. These data are consistent with the assumption that one dominant gene is responsible for the presence of viral antigens in the milk of C3Hf mice. This gene (Mtv-1) seems to be linked with the albino locus situated on chromosome 7; the recombination percentage was about 29. In the first experiment with Bc I mice a significant difference was found between the tumour ages of the mice with virus-positive milk and of the mice with virus-negative milk: all mice (18) with viral antigens in the milk developed mammary tumours at an age ranging from 7 to 18 months, whereas in only 7 out of 16 mice with virus-negative milk were mammary tumours found before the age of 21 months. Viral antigens were detectable (by RIA) in the tumours of mice of both subgroups; however, the amounts (mU/mg tumour) were significantly lower in the tumours derived from mice with virus-negative milk. Although MTV-L of C3Hf mothers could be transmitted to BALB/c mice by foster-nursing, viral antigens could not be detected in milk samples collected prior to the third lactation period; thus an influence on the data of extrachromosomally transmitted MTV-L is unlikely.
By immunodiffusion assay (ID-test) milk samples of mice of several strains and of F1-hybrids of the GR strain were tested for the presence of mammary tumour virus (MTV) antigens. The results clearly demonstrated that the presence of viral antigens in the milk of the first lactation period is restricted to mice harbouring endogenous MTV-GR. Viral antigens were detectable in about 50% of the milk samples collected during the first (occasionally the second) lactation periods of mice of the segregating backcross I (Bc I) populations: DBAfX(DBAfXGR), AKRX(AKRXGR), BALB/cX(BALB/cXGR) and C57BLX(C57BLXGR), indicating that one dominant gene is responsible for the presence of viral antigens in the milk of GR mice. The proposed gene symbol is Mtv-2. Milk samples from female mice of three different Bc II populations were tested for the occurrence of viral antigens. In the first Bc II: [BALB/cX(BALB/cXGR)]XBALB/c 33 out of 51 mice, descending from ID-positive mothers, had ID-positive milk and only one out of 71 mice, which were the progeny of ID-NEGATIVE Bc I mothers, was ID-positive. These results may be influenced by the MTV transmitted extrachromosomally via the milk of the mother. The two other Bx II populations were derived from Bc I fathers, either [BALB/cX(BALB/cXGR)] or [(BALB/cXGR)XBALB/c] f and BALB/c females. The results obtained with these Bc II populations suggested that 6 Bc I fathers were heterozygous for Mtv-2. Since the segregation ratio (60:29) in the Bc II population (progeny of these 6 Bc I male) deviates significantly from the expected 1:1 ratio, one may assume extrachromosomal transmission of MTV via the seminal fluid of the father to the progeny. A close correlation was found between the presence of MTV antigens in the milk and the occurrence of both early mammary tumours after hormone treatment and spontaneous mammary tumours before the age of 13 months. These results suggest that the early appearance of mammary tumours in the GR strain and the early expression of MTV antigens in the milk appear to be controlled by the same genetic factors.
Administration of bacterial lipopolysaccharides (LPS) to mice causes a rise in tissue and serum colony stimulating factor (CSF) levels and in bone marrow and splenic colony forming cells (CFC). Two inbred strains of mice differing in their response to LPS were used to study the genetic control of LPS induced granulopoietic responses: a high responder strain (C3H/eB) which reacts to LPS by an elevation in serum CSF and by an increase in splenic CFC levels, and a low responder strain (C3H/HeJ) which fails to show these responses. The ability to generate serum CSF after administration of LPS is controlled by a single autosomal dominant gene, while the splenic CFC response to LPS follows the characteristic patterns of a polygenic inheritance control. The associated relationships of CSF and CFC responsiveness have been investigated in backcross (F1 X C3H/Hej) and F2 mice. Most mice which generated high levels of CSF showed a high or intermediate CFC response and most mice which did not generate any detectable levels of serum CSF showed a low splenic CFC response. The results suggest that CSF may play a physiologic role in vivo as a granulopoietin. In addition it was shown that the genetic control mechanisms governing the CSF/CFC responses are determined by the lipid A-KDO portion of the LPS molecule, suggesting that lipid A is the active part of the LPS molecule in stimulating granulopoiesis.
Familial occurrence of fistula auris congenita (ear pits) is described in a Muslin kindred of Indian origin. The pedigree was traced through seven generations. The abnormality appeared in sixty individuals comparising equal number of males and females. No sexual dimorphism was indicated in the expression of the trait, which occurred bilaterally as a small pit just anterior to the crus at the root of the ascending helix. The abnormality was found to be inherited through an autosomal dominant gene with incomplete penetrance. The expression of the trait does not show any dosage effect.
Resistance to the organophosphate insecticide tetrachlorvinphos was examined in a house fly (Musca domestica L.) strain with an altered acetylcholinesterase (AChE) of decreased sensitivity to inhibition by the insecticide. Genetic tests showed that both resistance and the altered AChE were controlled by semi-dominant gene(s) on chromosome II. The gene for resistance was five crossover units from the mutant marker stubby wing (stw). A house fly strain was prepared in which resistance was introduced in to a susceptible stw strain by recombination. Biochemical assays revealed that the altered AChE was introduced along with resistance. Assays of the AChE of resistant and susceptible stw strains by two independent methods showed that the enzyme from resistant flies was 30 times more slowly inhibited by tetrachlorvinphos than the enzyme from susceptible flies.
An enzyme catalyzing the transfer of the glucosyl moiety of UDP-glucose to the 5-hydroxyl group of cyanidin-3-rhamnosyl-(1 leads to 6)-glucoside has been demonstrated in petal extracts of Silene dioica plants. This glucosyltransferase activity was not detectable in green parts of these plants. The enzyme activity is controlled by a single dominant gene M; no glucosyltransferase activity could be demonstrated in petals of m/m plants. The enzyme was purified eightyfold by PVP and Sephadex G50 chromatography. The glucosyltransferase had a pH optimum of 7.4, had a molecular weight of about 55,000, was stimulated by divalent metal ions, and had a "true Km" values of 0.5 x 10(-3) M for UDP-glucose and 3.6 x 10(-3) M for cyanidin-3-rhamnosylglucoside. Pelargonidin-3-rhamnosylglucoside also could serve as acceptor. The enzyme did not catalyze the glucosylation of the 5-hydroxyl group of cyanidin-3-glucoside, although in petals of M/- n/n mutants cyanidin-3,5-diglucoside is present. ADP-glucose could not serve as a glucosyl donor.
Mink Ldl antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ldl and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data.