SEARCH · PubMed Health

Results for “Inheritance Patterns”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 469 records · Page 26Linked to original sources

PubMed2005

Management strategies for patients with hereditary pancreatic cancer.

It is likely that hereditary factors play a role in 17% or more of pancreatic cancers. Ten percent of patients have a familial history that causes disease. Another 7% have a history of apparently "sporadic" pancreatic cancer patients carry a genetic mutation that causes the disease. Kindreds, with two or more family members who have been diagnosed with pancreatic cancer and who are first-degree relatives, are considered to have familial pancreatic cancer (FPC). The inheritance pattern for FPC is usually autosomal dominant; however, the penetrance (whether a gene carrier gets the disease) is variable. The lifetime cancer risk for a gene-carrying individual from a FPC kindred can range from 5% to 100%, depending upon the gene inherited and environment-gene interactions. Smoking is the chief environmental risk factor that influences penetrance of pancreatic cancer in these kindreds. Smoking increases the risk of cancer by more than threefold and decreases the age of onset by approximately 10 years. The precursor lesion to pancreatic cancer is pancreatic intraepithelial neoplasia (PanIN), which is graded I to III depending upon the severity of the neoplastic change. Surveillance for the early detection of cancer or intraepithelial neoplasia is possible in high-risk individuals and should be performed in centers with expertise. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography can help identify those patients who have intraepithelial neoplasia and thus may warrant a tissue diagnosis. Patients who have PanIN III (carcinoma in situ) can consider the option of pancreatectomy. The widespread and multifocal nature of PanIN changes throughout the entire pancreas in high-risk patients would make a total pancreatectomy preferable over a partial surgery. Careful selection of patients, the timing of the operation, and an experienced team of gastroenterologists, pancreatic surgeons, pathologists, and diabetologists are the keys to a good surveillance program and good outcomes for the patient.

Genetic Predisposition to Disease↗

PubMed2001

Aberrant methylation of donor genome in cloned bovine embryos.

Despite recent successes in cloning various animal species, the use of somatic cells as the source of donor nuclei has raised many practically relevant questions such as increased abortion rates, high birth weight and perinatal death. These anomalies may be caused by incomplete epigenetic reprogramming of donor DNA. Genome-wide demethylation occurs during early development, 'erasing' gamete-specific methylation patterns inherited from the parents. This process may be a prerequisite for the formation of pluripotent stem cells that are important for the later development. Here, we provide evidence that cloned bovine embryos may have impaired epigenetic reprogramming capabilities. We found highly aberrant methylation patterns in various genomic regions of cloned embryos. Cloned blastocysts closely resembled donor cells in their overall genomic methylation status, which was very different from that of normal blastocysts produced in vitro or in vivo. We found demethylation of the Bov-B long interspersed nuclear element sequence in normal embryos, but not in cloned embryos, in which the donor-type methylation was simply maintained during preimplantation development. There were also significant variations in the degree of methylation among individual cloned blastocysts. Our findings indicate that the developmental anomalies of cloned embryos could be due to incomplete epigenetic reprogramming of donor genomic DNA.

Animals↗

PubMed2002

Genetic dissection of transcriptional regulation in budding yeast.

To begin to understand the genetic architecture of natural variation in gene expression, we carried out genetic linkage analysis of genomewide expression patterns in a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae. Over 1500 genes were differentially expressed between the parent strains. Expression levels of 570 genes were linked to one or more different loci, with most expression levels showing complex inheritance patterns. The loci detected by linkage fell largely into two categories: cis-acting modulators of single genes and trans-acting modulators of many genes. We found eight such trans-acting loci, each affecting the expression of a group of 7 to 94 genes of related function.

Chromosome Mapping↗

PubMed1995

Intermediate inheritance of Tourette syndrome, assuming assortative mating.

Segregation analysis incorporating assortative mating was used to test for major locus inheritance of Tourette syndrome in a single large pedigree containing 182 members. The analysis provided evidence of a major locus with an intermediate inheritance pattern for which the penetrance was estimated from the data as 28% in heterozygotes and 98%-99% in homozygotes. A significant assortative mating correlation was estimated from the data as 70%-79%. In contrast, when assortative mating was not included in the model, intermediate inheritance was not inferred. If, in addition, constancy of the allele frequencies across generations was not assumed, Mendelian transmission was rejected. Each subject, affected or unaffected, was assigned a score reflecting the presence and severity of symptoms. Higher means scores in affected homozygotes than in affected heterozygotes suggested greater severity in homozygotes: genotype information was obtained from genotype probabilities computed assuming intermediate inheritance.

Adolescent↗

PubMed2001

Differential expression of the GTL2 gene within the callipyge region of ovine chromosome 18.

The inheritance pattern of the skeletal muscle hypertrophy phenotype caused by the callipyge gene has been characterized as polar overdominance. We hypothesized that this trait may be caused by a gain or loss of gene expression because of the reversible nature of the phenotype in paternal vs. maternal inheritance. Suppression subtraction cDNA probes were made from skeletal muscle mRNA of normal (NN) and callipyge (C(Pat)N(Mat)) animals and hybridized to Southern blots containing bacterial artificial chromosomes (BACs) that comprise a physical contig of the callipyge region. The CN-NN probes hybridized to two ovine and seven bovine BACs. Sequence analysis of fragments within those BACs indicated short regions of similarity to mouse gene trap locus (gtl2). Northern blots analysis of RNA from hypertrophy-responsive muscles show a population of GTL2 mRNA centred around 2.4 kb that were abundantly expressed in 14-day prenatal NN and C(Pat)N(Mat) lambs but were down-regulated in day 14 and day 56 postnatal NN lambs. The expression of GTL2 remained elevated in 14- and 56-day-old C(Pat)N(Mat) lambs as well as in 56-day-old N(Pat)C(Mat) and CC lambs. Expression of GTL2 in the supraspinatus, which does not undergo hypertrophy, was very low for all genotypes and ages. Isolation of cDNA sequences show extensive alternative splicing and a lack of codon bias suggesting that GTL2 does not encode a protein. The mutation of the callipyge allele has altered postnatal expression of GTL2 in muscles that undergo hypertrophy and will help identify mechanisms involved in growth, genomic imprinting and polar overdominance.

Alternative Splicing↗

PubMed1999

Patterns of genetic inheritance.

Neonatal nurses need to understand the basic patterns of genetic transmission. This article, the first in a series, provides an overview of Mendel's laws and discusses five types of transmission: single gene inheritance, chromosomal inheritance, multifactorial inheritance, cytoplasmic inheritance, and somatic cell mutations.

Extrachromosomal Inheritance↗

PubMed1997

Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.

Adult↗

PubMed2001

Identification of genetic loci associated with paralysis, inflammation and weight loss in mouse experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is an inducible inflammatory and demyelinating disease of the central nervous system (CNS). Susceptibility to this disease is heritable and is demonstrated by the development of an ascending paralysis accompanied by a loss in body wt 2-3 weeks following immunization with proteins derived from CNS myelin. In a previous genetic analysis of susceptibility to EAE in a cross between susceptible SJL/J mice and resistant B10.S mice, we found suggestive evidence of linkage with disease susceptibility at the telomeric end of chromosome 2 and in the central region of chromosome 3. To define these associations more precisely and to investigate the genetic factors controlling measurable phenotypes of EAE, we performed a new analysis with a larger number of mice. The results now indicate that the chromosome 2 locus significantly influences EAE-related weight loss (P = 6.7 x 10(-5)) and that the chromosome 3 locus is linked with the development of paralysis. In addition, an intriguing inheritance pattern was revealed in which female backcross mice generated from B10.S female x (B10.S x SJL/J)F(1) male parents experienced significantly more EAE-related weight loss (P = 1.2 x 10(-4)) than females generated from F1 female x B10.S male parents. After controlling for this inheritance, a new locus at the centromeric end of chromosome 8 was identified that significantly influences both the development of paralysis (P = 8.2 x 10(-6)) and the incidence of CNS inflammation (P = 7.0 x 10(-5)) in EAE.

Animals↗

PubMedDate not supplied

Influence of parental genotype on plastid inheritance in Medicago sativa.

Research using chlorophyll-deficient mutants has shown that plastids are inherited biparentally in Medicago sativa L. (alfalfa). Variation in plastid transmission behavior was observed among crosses in earlier studies, but it was not determined whether this variation was under genetic control. In my research, genetic analyses of the frequencies of normal (G), chlorophyll-deficient (CD), and sectored (G and CD) progenies produced from G x CD crosses demonstrated that plastid inheritance patterns in alfalfa are influenced by both maternal and paternal genotypes. A strong paternal bias in plastid transmission existed in the majority of crosses despite the potential developmental disadvantages associated with paternally contributed CD plastids. The high frequencies of uniparental progenies suggest that genetic control of plastid inheritance in alfalfa may be exerted through effects on the number and distribution of maternal and paternal plastids early in embryo development.

Chlorophyll↗

PubMed1992

von Willebrand disease family studies: comparison of three methods of analysis of the von Willebrand factor gene polymorphism related to a variable number tandem repeat sequence in intron 40.

A region with a variable number of tandem ATCT repeats (VNTR) has previously been localized within intron 40 of the von Willebrand factor (vWF) gene. In the present report we describe the use of this polymorphism as a genetic marker to study the inheritance pattern in five families affected with various types of von Willebrand disease (vWD): types I, IIA, IIB, IIC and the newly characterized variant with totally defective FVIII binding. Three means of investigation previously reported, all using polymerase chain reaction (PCR) amplification of this vWF gene region, were compared in terms of informativeness. The two direct single-step procedures analysing only partial sequences of the VNTR region turned out to be less informative (three studies informative out of five) than the third method characterizing the variability of the whole VNTR sequence. This latter approach, based on the analysis of the Alu I restriction pattern of the VNTR region, was informative in all the families investigated, therefore avoiding the need to combine it with other genetic marker studies for efficient gene tracking. In conclusion, this two-step (PCR and digestion) method is the most informative for the characterization of the inheritance of the different subtypes of vWD and for the prenatal diagnosis of its severe forms.

Alleles↗

PubMed2004

Thyroid hormone binding protein abnormalities in patients referred for thyroid disorders.

BACKGROUND & OBJECTIVES: Thyroid hormone binding protein (THBP) abnormalities are the major cause of discordance in commonly performed total thyroxine (T4) and thyrotropin (TSH) estimations, though these do not interfere with thyroid hormone action. Determination of such abnormalities in patients showing discordant thyroid function tests (TFTs) is diagnostically important as it eliminates equivocal assessment of thyroid function and treatment especially where proper methodology for free T4 (FT4) estimation is not available. This study was undertaken to analyse the THBP abnormalities in the population attending thyroid clinic. Family members of affected patients were also screened to study the inheritance of quantitative TBG abnormalities. METHODS: Blood samples of 15000 consecutive patients over a period of 4 years (1994-1997) were tested for thyroid function. THBP abnormalities were studied using polyacrylamide gel electrophoresis autoradiography. Serum thyroxine binding globulin (TBG), free and total T4, total tri-iodothyronine (TT3) were assayed by radioimmunoassay methods. RESULTS: In our screening of 15,000 thyroid patients over a four year period, we found the presence of complete and partial TBG deficiency and TBG excess to be 1:2,500, 1:200 and 1:15,000 respectively. Our study on the families of three affected patients revealed X-chromosome linked inheritance pattern of TBG deficiency in two families and TBG excess in one family. INTERPRETATION & CONCLUSION: Our study suggests that it would be beneficial to rule out THBP abnormalities before interpreting results of TFTs, particularly when there is large discrepancy between T4 and TSH levels. In case of inherited THBP abnormalities, the family members of the affected individual should also be screened to avoid misdiagnosis and erroneous treatment in case they develop thyroid dysfunction in future.

Autoradiography↗

PubMed1984

Segregation patterns of polymorphic restriction sites of the gene encoding the alpha subunit of human chorionic gonadotropin in trophoblastic disease.

The gene encoding the alpha subunit of human chorionic gonadotropin contains at least two polymorphic sites in its 3' flanking region detected by restriction enzymes HindIII and EcoRI. We used these polymorphic sites as markers of tissue genotype in normal placenta, hydatidiform mole, choriocarcinoma, and peripheral leukocytes. As expected, inheritance patterns of most hydatidiform moles showed only a paternal genetic contribution. However, one uncommon DNA polymorphism pattern, homozygosity for the absence of the EcoRI site and the presence of the HindIII site, predominated in choriocarcinoma. Thus, our results suggest that moles which have this uncommon polymorphism pattern appear particularly likely to develop into choriocarcinoma.

Choriocarcinoma↗

PubMed1996

Autosomal dominant zonular cataract with sutural opacities in a four-generation family.

PURPOSE: We identified and examined four generations of a family with coexisting autosomal dominant zonular cataracts and sutural opacities and sought to determine their genetic basis. METHODS: Twenty-four of the 48 members in the family were examined. Systemic and ocular histories were obtained, and a detailed ophthalmic examination was performed. From each individual, 20 ml of blood was drawn for linkage studies with microsatellite markers in regions to which zonular cataracts had previously been localized (chromosomes 1, 2, and 16). RESULTS: Individuals of the first generation were reportedly asymptomatic. Several members of the second generation had morphologically identical zonular cataracts. Affected members of the third generation showed morphologic heterogeneity, with the zonular opacity varying from a uniform lamella to a segregation of dots. A high degree of consanguinity in the second generation suggested recessive inheritance with a pseudodominant inheritance pattern. However, examination of one member of the asymptomatic first generation disclosed senile cataractous changes superimposed on a faint zonular cataract enclosing sutural opacities and a pulverulent fetal nucleus. The latter findings were reconfirmed to be present in affected members of all generations, suggesting an autosomal dominant mode of inheritance. Initial efforts at linkage analysis excluded the gene locus causing this cataract from the Duffy, haptoglobin, and gamma-crystallin regions. CONCLUSIONS: The cataract in this family is both phenotypically and genetically distinct from previously described and mapped cataracts.

Adolescent↗

PubMed2001

[Microspherocytosis. Erythroid profile and its relation with different laboratory tests].

Hereditary spherocytosis (HS) is a congenital and hemolytic anemia characterized by the presence of microspherocytes on the peripheral blood film and negative Coombs test. Although HS is a heterogeneous syndrome in terms of clinical severity, inherents and underlying molecular defects (deficiency of membrane skeleton proteins), typical HS has a dominant inheritance pattern and presents anemia, jaundice and splenomegaly. The purpose of this study was to present our experience and to establish the relationship between hematological and biochemical parameters and osmotic fragility and autohemolysis, all of them considered as traditionally available tests. In our environment, HS is the second most common inherited anemia after beta thalassemia trait. The diagnosis was based on osmotic fragility measurements, autohemolysis test and microspherocytes in 47 patients (45 of latin, 2 of saxon origin); 12 patients had a negative family history. Mean values: RBC (x 10(12)/L) and Hb (g/dL): children (22): 3.84/10.5; adults (25): female (13): 3.54/10.59; masculine (12): 4.65/13.15. Autohemolysis (average %) was very much increased (15.54) and it was corrected by the addition of glucose (4.07). Median osmotic fragility (average g/dL) was increased in both fresh (0.48) and incubated blood (0.65). 76.5% children and 26.7% adults had absence of haptoglobin. Reticulocytes, indirect bilirubin and LDH were increased (average values 336.35 x 10(9)/L, 36.25 mmol/L and 236.48 UI/L, respectively). Microcytosis, spherocytosis, polycromatophylia, acanthocytosis, basophilic stippling, pincered cells were observed in 43, 41, 41, 12, 11, 1 patients respectively. Morphologic alterations were more marked in children. The laboratory findings seemed more a consequence of microcytosis than of spherocytosis.

Adolescent↗

PubMed2002

Hirschsprung, RET-SOX and beyond: the challenge of examining non-mendelian traits (Review).

Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a common hereditary disorder causing intestinal obstruction, thereby showing considerable phenotypic variation in conjunction with complex inheritance. Moreover, phenotypic assessment of the disease has been complicated since a subset of the observed mutations is also associated with several additional syndromic anomalies. Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery. For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated.

DNA-Binding Proteins↗

PubMed2002

Vestibular dysfunction in the epistatic circler mouse is caused by phenotypic interaction of one recessive gene and three modifier genes.

Vestibular dysfunction is a frequent clinical problem, leading to dizziness and imbalance. Genes play an important role in its etiology, but the genetics are complex and poorly understood. In this study we have analyzed the complex inheritance pattern in the Epistatic circler mouse, which shows circling behavior indicative of vestibular dysfunction in the mouse. This phenotype exists in a proportion of the F2-generation from an intercross between C57L/J and SWR/J mouse strains. Genetic investigation indicates that the circling behavior is caused by a major recessively inherited gene derived from the SWR/J strain (the Ecs-gene) in combination with at least three different modifier genes derived from C57L/J (the Ecl-genes). Genetic mapping made it possible to localize the Ecs-gene to chromosome 14 and the Ecl-genes to chromosome 3, 4, and 13. This study illustrates the feasibility of identifying genes for multifactorial traits in mice.

Animals↗

PubMed1988

Acrodysostosis: report of a 13-year-old boy with review of literature and metacarpophalangeal pattern profile analysis.

We report on a 13-yr-old boy with acrodysostosis, a review of 30 cases in the literature, and metacarpophalangeal pattern profile (MCPP) analysis. The prominent manifestations (present in greater than 75% of cases) of this condition include nasal and maxillary hypoplasia, peripheral dysostosis, first ray hyperplasia of the foot, acromesomelic brachymelia, decreased interpedicular distance, advanced skeletal maturation and mental retardation. Results of chromosome studies have been normal. An autosomal dominant inheritance pattern was reported in two families. Maternal and paternal ages were 2 and 3 yr, respectively, above the average age of the general parent population, which suggests that advanced parental age may be a factor in the cause of this condition. A characteristically abnormal MCPP was found in our patient and in 16 additional cases studied from the literature. A mean MCPP was developed for the syndrome. MCPP analysis may be useful as a diagnostic tool in patients suspected to have acrodysostosis.

Adolescent↗

PubMed2004

Desmin myopathy.

Desmin myopathy is a recently identified disease associated with mutations in desmin or alphaB-crystallin. Typically, the illness presents with lower limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial, bulbar and respiratory muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks and arrhythmias resulting in premature sudden death. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing amorphous eosinophilic deposits seen as granular or granulofilamentous material on electron microscopic examination. Immuno-staining for desmin is positive in each region containing abnormal structures. The inheritance pattern in familial desmin myopathy is autosomal dominant or autosomal recessive, but many cases have no family history. At least some, and probably most, non-familial desmin myopathy cases are associated with de novo desmin mutations. Age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Multiple mutations have been identified in the desmin gene: point substitutions, insertion, small in-frame deletions and a larger exon-skipping deletion. The majority of these mutations are located in conserved alpha-helical segments of desmin. Many of the missense mutations result in changing the original amino acid into proline, which is known as a helix breaker. Studies of transfected cell cultures indicate that mutant desmin is assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. Disease-associated desmin mutations in humans or transgenic mice cause accumulation of chimeric intracellular aggregates containing desmin and other cytoskeletal proteins. alphaB-crystallin serves in the muscle as a chaperone preventing desmin aggregation under various forms of stress. If mutated, alphaB-crystallin may cause a myopathy similar to those resulting from desmin mutations. Routine genetic testing of patients for mutations in desmin and alphaB- crystallin genes is now available and necessary for establishing an accurate diagnosis and providing appropriate genetic counselling. Better understanding of disease pathogenesis would stimulate research focused on developing specific treatments for these conditions.

Amino Acid Sequence↗