SEARCH · Search PubMed

Results for “Segregation analysis”

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.

SourceResearch connectionFrom yearThrough year

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

At least 1,603 records · Page 89Linked to original sources

PubMed1999

CD4 and CD8 T lymphocyte inheritance. Evidence for major autosomal recessive genes.

The CD4/CD8 ratio has long been used for the follow-up and monitor of many infectious diseases. Following the demonstration in 1983 that the CD4/CD8 ratio in the mouse is under genetic control, it was subsequently shown to be controlled by a major locus in man. To define the mode of inheritance of the CD4/CD8 ratio, we addressed the absolute number of CD4 and CD8 cells in a large unselected control sample and in members of 70 nuclear families. Pedigrees of nuclear families were analyzed by complex segregation analysis. Data was adjusted prior to this analysis to remove the effects of relevant covariates. The non-genetic-transmission and the multifactorial model could be easily rejected for both CD4 and CD8 cells. Among the different inheritance models, involving both a major gene and a multifactorial (MFT) component, a major autosomal recessive gene with a residual MFT effect controlling the high number of CD4 and a major autosomal recessive gene with a residual MFT effect controlling the high number of CD8 cells were the significantly best-fitting ones. Our findings have some practical implications. Among all, the knowledge of the CD4+ cell number and the proportion between CD4+ and CD8+ T cells could be a useful parameter in predicting human immunodeficiency virus infection outcome.

Adolescent↗

PubMed1999

Inheritance of heart rate variability: the kibbutzim family study.

Heart rate variability (HRV) measures are associated with coronary heart disease incidence and mortality. Therefore insight into the genetic and environmental determinants of these measures may have clinical relevance. We assessed the role of genetic and environmental factors of time domain and frequency domain HRV indices. Participants were 451 kibbutz members, aged 15 and up, belonging to 80 families. HRV indices were calculated from Holter recordings measured over 5 min. Our data indicate that for the two time- and four frequency domain indices, a mixture of two normal distributions fit the data significantly better than a single normal distribution (P<0.05). We used complex segregation analysis to infer the modes of inheritance of these HRV measures. We found evidence for possible involvement of a recessive major gene in the inheritance of the root mean square of successive differences in RR intervals (RMSSD), which is predominantly vagally mediated. A putative major gene explains 28%-34% of the adjusted inter-individual variability. The SD, determined by a mixture of mechanisms, is influenced by environmental and polygenic effects, but not by a major gene. The findings regarding the heritability of the frequency domain indices were not conclusive. However, the involvement of genetic factors was not rejected. Additional studies in extended families are needed to confirm the involvement of major genes in the determination of the autonomic activity.

Adolescent↗

PubMed2026

Expansion of the allelic and phenotypic spectrum of MED25-related developmental disorder: novel compound heterozygous variants with structural domain implications.

MED25-related developmental disorder (Basel-Vanagaite-Smirin-Yosef syndrome) is a rare autosomal recessive disorder, defined by severe neurodevelopmental delay, corpus callosum abnormalities, ocular involvement, epilepsy, and marked facial appearance. MED25 pathogenic variants interfere with the functioning of the Mediator complex, which is responsible for RNA polymerase II transcription. We report a 9-year-old girl who presents with significant global developmental delay, agenesis of the corpus callosum, congenital cataracts, epilepsy, hypotonia, musculoskeletal abnormalities, and typical craniofacial features. Trio-based whole-exome sequencing revealed compound heterozygous variants in MED25: a maternally transmitted truncating variant (c.1366 C > T; p.Gln456*) and a paternally inherited missense variant (c.430 C > T; p.Leu144Phe). The new classification of the missense variant as potentially pathogenic is supported by a systematic ACMG re-evaluation supported by segregation analysis, phenotypic specificity, computational prediction, and structural localization in the MED25 Activator Interaction Domain (ACID). Comparative phenotypic analyses show strong agreement with reported cases but add more data to fine-tune clinical spectrum. This article broadens the allelic and phenotypic spectrum of MED25-related developmental disorder and highlights the need for comprehensive evaluation across molecular, structural, and phenotypic pathways to elucidate variant signature in rare genetic disease models correctly.

Humans↗

PubMed2004

Isolation and physical mapping of sex-linked AFLP markers in nile tilapia (Oreochromis niloticus L.).

Gynogenetically produced XX and YY Nile tilapia (Oreochromis niloticus) and diploid control groups were screened for amplified fragment length polymorphisms (AFLPs) to search for sex-linked or sex-specific markers. Family-level bulked segregant analysis (XX and YY gynogenetic family pools) and individual screening (XX and YY gynogenetics and XX and XY control individuals) identified 3 Y-linked (OniY425, OniY382, OniY227) and one X-linked (OniX420) AFLP markers. OniX420 and OniY425 were shown to be allelic. Single locus polymerase chain reaction assays were developed for these markers. Tight linkage was demonstrated between the AFLP markers and the sex locus within the source families. However, these markers failed to consistently identify sex in unrelated individuals, indicating recombination between the markers and the sex-determining loci. O. niloticus bacterial artificial chromosome clones, containing the AFLP markers, hybridized to the long arm of chromosome 1. This confirmed previous evidence, based on meiotic chromosome pairing and fluorescence in situ hybridization probes obtained through chromosome microdissection, that chromosome pair 1 is the sex chromosomes.

Animals↗

PubMed2026

Rapid Agrobacterium-mediated transformation and high-efficiency regeneration of finger millet (Eleusine coracana) for crop improvement.

Finger millet (Eleusine coracana) is a nutritionally important and climate-resilient cereal cultivated in rainfed regions of India and Eastern Africa, yet its genetic improvement has been limited by the lack of efficient and reproducible transformation systems. In this study, we developed a rapid and efficient Agrobacterium tumefaciens-mediated transformation and regeneration system using shoot apical meristem (SAM) explants, enabling direct, callus-free shoot organogenesis. Optimal regeneration and shoot elongation were achieved on Murashige and Skoog (MS) medium supplemented with 3.5 mg L⁻1 6-benzylaminopurine (BAP), 1.5 mg L⁻1 kinetin, 0.1 mg L⁻1 2,4-dichlorophenoxyacetic acid (2,4-D), and 0.2 mg L⁻1 gibberellic acid (GA₃). Genotype-dependent responses were observed, with PR-202 requiring 2 mg L⁻1 AgNO3 to reduce phenolic browning, whereas VL-376 regenerated efficiently without AgNO3. Transformation efficiencies of 30-32% were achieved in PR-202 and VL-376, respectively, by optimising infection and co-cultivation conditions, including reduced MS salt strength and pre-incubation of Agrobacterium. Molecular analyses, including PCR and Southern blot hybridisation, confirmed stable T-DNA integration in independent lines, while segregation analysis of T₁ progenies demonstrated Mendelian inheritance of the transgene. In addition, CRISPR/Cas9 constructs targeting EcCKX2 were successfully introduced via Agrobacterium, demonstrating the suitability of this system for genome engineering applications. Overall, this optimised SAM-based protocol provides a rapid (45-50 days), efficient, and reproducible platform for stable genetic transformation in finger millet and establishes a strong foundation for transgenic research and future genome editing studies in this underutilized crop.

Eleusine↗

PubMed2000

New insights and candidate genes and their implications for care of patients with hereditary prostate cancer.

A positive family history is a risk factor for prostate cancer. Most studies based on segregation analysis suggest autosomal dominant transmission of susceptibility genes. Multiple loci on chromosome 1 and chromosome X have been associated with prostate cancer by linkage analysis. The candidate gene approach has also revealed multiple genetic markers that are associated with increased risk for the disease. The genetic studies in prostate cancer suggest there are multiple genes involved in the development and progression of prostate cancer.

Case-Control Studies↗

PubMed1992

Further evidence of the SA gene as a candidate gene contributing to the hypertension in spontaneously hypertensive rat.

We have recently reported that the allele of the SA gene of the Spontaneously hypertensive rat (SHR) has a capacity to influence blood pressure in a F2 rat population prepared from SHR and Wistar-Kyoto rat. In the present study, we have undertaken a similar genetic co-segregation analysis of the F2 rat population prepared from SHR and Lewis rat. The result indicated that, although overall effects of the SA gene genotypes on blood pressure were not significant, a correlation of the genotypes of the SA gene with blood pressure was significantly observed in the female rats of this population. The present results further strengthen our hypothesis that the SA gene, or a gene closely linked to this gene, has a capacity to influence blood pressure.

Animals↗

PubMed1993

A familial/genetic study of plasma serine and glycine concentrations.

Plasma serine and glycine concentrations were assayed in a sample of 28 nuclear families (n = 108). Complex segregation analysis of these familial data reveals significant genetic control of concentrations via a single major gene locus. The serine and glycine metabolizing enzyme serine hydroxymethyltransferase (SHMT) is suggested as the most likely candidate for this single major gene locus.

Dopamine↗

PubMed1987

Differential susceptibility to actively induced experimental allergic encephalomyelitis and experimental allergic orchitis among BALB/c substrains.

Experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) are animal models of organ-specific autoimmune disease. In this study, BALB/cByJ and BALB/cAnNCr mice were susceptible to both autoimmune diseases whereas BALB/cJ subline mice were resistant. Disease resistance in BALB/cJ mice did not appear to be a reflection of either (i) a nonspecific generalized impairment of cellular immunity or (ii) an alteration in the phenotypic expression of Bordetella pertussis-induced histamine sensitization, a phenotype which has been shown to be associated with susceptibility to both diseases. Susceptibility to both EAE and EAO was inherited as a dominant trait in F1 hybrid animals. Segregation analysis in a (BALB/cByJ X BALB/cJ) X BALB/cJ backcross population suggested that disease resistance may be associated with a single genotypic difference in a common regulatory gene affecting susceptibility to both diseases. Linkage analysis of the backcross population failed to demonstrate an association of disease resistance with the mutant raf-1b allele carried by BALB/cJ mice. The results of these studies support previous observations that multiple genotypic differences may in fact exist in mice of the BALB/cJ subline and that such differences play a significant role in the genetic control of susceptibility to EAE and EAO.

Animals↗

PubMed1990

Inosine triphosphate pyrophosphohydrolase deficiency in a kindred with adenosine deaminase deficiency.

A complete deficiency of inosine triphosphate pyrophosphohydrolase (ITPase) has been identified, together with high concentrations (mean 157 mumol/l) of the unusual nucleotide ITP, in the erythrocytes of 3 members of a consanguineous United Kingdom kindred. The defect has been noted previously in North America and Sweden, but even in presumed homozygotes some residual ITPase activity was reported. Homozygosity for the defect has not been associated previously with any clinical abnormality. In this kindred it was co-existent with adenosine deaminase (ADA) deficient severe combined immunodeficiency. Since the genes for both ITPase and ADA are localised on the same chromosome, segregation analysis of ITPase and ADA activity was undertaken in available kindred members. The results confirmed an autosomal recessive mode of inheritance for ITPase deficiency, but suggested that the co-existence with ADA deficiency was coincidental.

Adenosine Deaminase↗

PubMed1994

Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family.

Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle.

Apolipoprotein B-48↗

PubMed1987

Expression of chimeric genes in Caenorhabditis elegans.

We have shown the expression of transformed genes in the nematode Caenorhabditis elegans using a new gene fusion system. Vectors consisting of the flanking regions of a collagen gene (col-1) or a major sperm protein gene of C. elegans fused to the Escherichia coli uidA gene, encoding beta-glucuronidase, were microinjected into worms and found to be propagated as high-copy extrachromosomal tandem arrays. We have detected beta-glucuronidase activity in transformed lines, and have shown that the activity is dependent upon the correct reading frame of the construction and on the presence of the worm sequences. The enzyme activity was shown to be encoded by the chimeric beta-glucuronidase gene by co-segregation analysis and by inactivation with specific antisera. Expression is at a very low level, and seems to be constitutive. We have used histochemical techniques to visualize the enzyme activity in embryos.

Animals↗

PubMed1975

Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds.

A newly recognized familial hyperlipoproteinemia, familial hyper-alpha-lipoproteinemia, is described in 18 kindreds. Affected probands and relatives had distinctive elevations of alpha-lipoprotein cholesterol (C-HDL), slight elevations of total cholesterol, no elevation of LDL and VLDL cholesterol, and normal triglyceride levels. The proband and at least one additional first degree relative had distinctive elevations of C-HDL in 16 of 18 kindreds. Simple segregation analysis involving 84 offspring of 22 hyper-alpha X normal-alpha matings from these 16 kindreds revealed a ratio of hyper-alpha to normal of 37:47, a ratio not significantly different from 1:1 (chi 2(1) = 1.2), the ratio consistent with autosomal dominant transmission. Despite the suggestion of a major gene effect by this analysis, evaluation of the C-HDL distribution in kindred members failed to reveal bimodality, and familial correlation analysis revealed no parent-offspring correlation. The present data suggest that an environmental cause common to sibships is possibly important in causing the disorder. Longevity analysis demonstrated elongation of life expectancy for kindred members, and there was an apparent rarity of premature cardiac events.

Adolescent↗

PubMed1981

Genetic transmission of isoapolipoprotein E phenotypes in a large kindred: relationship to dysbetalipoproteinemia and hyperlipidemia.

The largest reported kindred of a proband with type III hyperlipoproteinemia was investigated by assessment of lipid and lipoprotein levels and very low density lipoprotein (VLDL) isoapolipoprotein E distributions in all accessible family members (56% of the 124 living blood relatives and 59% of the 37 spouses). The results confirm in this kindred a trimodal distribution of apoE3/E2 ratios, and segregation analysis of 16 informative matings classified according to E3/E2 ratio demonstrated classical Mendelian inheritance of the autosomal codominant type: the E3/E2 ratio is determined by two alleles, apoE3d and apoE3n, which produce three phenotypes apoE3-D, apoE3-ND, and apoE3-N, corresponding to the low, intermediate, and high modes, respectively. Vertical transmission of the apoE3-D phenotype occurred in two branches of the second generation. In both instances this represented pseudodominance; i.e., products of heterozygous (apoE3-ND) x homozygous (apoE3-D) matings. Hyperlipidemia (defined as a low density lipoprotein cholesterol and/or plasma triglyceride level exceeding the respective age-, sex-, and sex-steroid-specific 95th percentiles derived from Lipid Research Clinics population studies) was present in 15 blood relatives in multiple lipoprotein patterns, consistent with the presence of familial combined hyperlipidemia in this kindred. Eight of nine members with the apoE3-D phenotype had either type III hyperlipoproteinemia or, in the absence of hyperlipidemia, beta-VLDL and at least marginally cholesterol-rich VLDL (VLDL-cholesterol/plasma triglyceride greater than 0.25) (defined as dysbetalipoproteinemia). The ninth such member, the only child with this phenotype, was normal. beta-VLDL and marginally cholesterol-rich VLDL was seen in but one of six hyperlipidemic family members of phenotype apoE3-ND, in none of seven hyperlipidemic blood relatives of phenotype apoE3-N, in no normolipidemic family members of phenotype apoE3-ND or apoE3-N, and in no spouses (three of whom were hyperlipidemic and nine of phenotype apoE3-ND). Thus, among adult members of the O'D kindred the apo3-D phenotype was nearly specifically associated with dysbetalipoproteinemia or, when hyperlipidemia was present, type III hyperlipoproteinemia.

Adolescent↗

PubMed1993

Hereditary necrotising myelopathy in Kooiker dogs.

A retrospective clinicopathological study of a neurological disorder in 22 Kooiker dogs (Dutch decoy dog) was made. The disease was found to occur equally in both sexes and clinical signs began at three to 12 months old. Physical examination revealed a progressive paresis of the hindlimbs. Post mortem examination showed symmetrical areas of malacia in the ventral, lateral and dorsal white matter of the spinal cord. In one dog dorsal white matter was spared. Cervical segments C4 to C8 were involved in all subjects. Rostral and caudal to these areas, Wallerian degeneration was prominent. The disease has much in common with similar myelopathies in the Afghan hound and the rottweiler. Indications of heritability were the similarity in clinical and pathological findings, the age of onset of the disease, and the significantly higher inbreeding coefficient in the patients than in the breed population (P = 0.001). All patients were descended from one pair. Segregation analysis suggested inheritance involving a simple autosomal recessive trait.

Animals↗

PubMed1989

A susceptibility locus for multiple sclerosis is linked to the T cell receptor beta chain complex.

Inheritance of T cell receptor beta chain (TCR beta) genes was analyzed in families of 40 sibling pairs concordant for the relapsing-remitting form of multiple sclerosis (MS). TCR beta haplotypes were determined by segregation analysis of polymorphic markers within the TCR beta complex. The mean proportion of TCR beta haplotypes identical by descent (IBD) inherited by MS sibling pairs was significantly increased compared with expected values (means test, p less than 0.004), whereas the distribution of haplotype sharing was random when MS patients were compared with their unaffected siblings. Furthermore, one allelic form of a TCR beta variable region gene segment was overrepresented on MS chromosomes compared with those parental chromosomes not transmitted to MS offspring both in the MS sibling pair families and in a second group of families containing only one individual affected with MS. These results demonstrate that a gene within the TCR beta complex or a closely linked locus influences susceptibility to MS.

DNA Probes↗

PubMed1987

Delusional depression: further evidence for genetic contribution.

To quantify the contribution of genetic factors in the pathogenesis of delusional depression, the incidence of major depression in the first degree relatives of 77 delusional, 76 nondelusional depressive patients, and 153 age- and sex-matched controls was calculated in a case-control study. The morbid risk for psychiatric disorders, including major depression and bipolar I disorder, did not distinguish the two proband groups. The segregation analysis showed that the model of multifactorial inheritance fits best to our results. Heritability was estimated on the basis of a threshold model for multifactorial inheritance, and a high contribution of genetic factors for both subgroups was found.

Adult↗

PubMed1990

Assignment of an erbB-like DNA sequence to linkage group VI in fishes of the genus Xiphophorus (Poeciliidae).

The inheritance of 23 protein polymorphisms was compared with the inheritance of a DNA restriction fragment length polymorphism (RFLP) of a strongly cross-hybridizing erbB-related sequence, epidermal growth factor receptor-like-1 (EGFRL1), in Xiphophorus clemenciae X X. milleri-derived backcross hybrids. Two polymorphic bands were noted in this cross with a v-erbB probe after PstI digestion: a 10-kilobase (kb) band in X. clemenciae and a 9-kb band in X. milleri. Joint segregation analysis of the RFLPs and protein polymorphisms indicate that this erbB-related sequence can be assigned to Xiphophorus linkage group VI, which also comprises genes coding for glutamine synthetase (GLNS), nucleoside phosphorylase-2 (NP2), and transferin (TF). We have designated this RFLP as alleles at a locus called EGFRL1 because of very strong cross-hybridization with the v-erbB probe, known to be homologous to the mammalian EGFR gene. This mapping assignment is the first autosomal linkage of an oncogene sequence reported in fish, which provide a large number of genetically controlled experimental tumor models.

Animals↗