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At least 217 records · Page 12Linked to original sources
PubMed1988

Genetic analysis of human breast cancer: implications for family study designs.

Genetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and gene-environment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.

Breast Neoplasms↗
PubMed2005

[Clinical pathologic studies and genetic analysis of a female Duchenne muscular dystrophy family].

OBJECTIVE: To investigate the clinical features of female Duchenne muscular dystrophy(DMD), and find out the onset mechanism. METHODS: The clinical manifestations of a female DMD family were followed; the immunofluorescence studies on muscle system and the genetic analysis were carried out. RESULTS: The clinical manifestations and results of relevant examinations on the DMD woman in this family were in accordance with the typical characteristics of DMD. The 39-year-old mother of this proband was noted to have a clinical feature resembling that of Becker muscular dystrophy (BMD), and the immunofluorescence analysis revealed that dystrophin positive fibers and negative fibers co-existed in her muscle. The dystrophy genetic analysis of the family indicated non-deletions. The mother's karyotype was found to be normal. CONCLUSION: The 39-year-old female patient's clinical manifestations were similar to BMD, and only one third of her fibers were dystrophin-positive. The present authors assume that the skewed pattern of X inactivation is the likely mechanism, because the karyotype is normal.

Adult↗
PubMed1995

Genetic analysis of human DNA recovered from minute amounts of serum or plasma.

A rapid and inexpensive method is described where a small amount of serum or plasma was used as the source of DNA for genetic analysis. Using a silica gel matrix DNA was isolated from 50 microliters of archived serum or plasma. The specimens were collected from 13 individuals at two separate time points 3-6 years apart. The polymorphic region of second exon of the MHC class II gene HLA DQA1 was amplified using the polymerase chain reaction (PCR) to sufficient quantities to permit genetic analysis using allele-specific oligonucleotides (ASO). Allelic typing of each specimen was performed and the reproducibility of the method was demonstrated in that in all 13 cases the two independently isolated specimens produced the identical ASO binding patterns. No qualitative difference was noted in the amplified product generated from plasma or serum. This study demonstrates (a) that minute amounts of serum or plasma are able to provide sufficient quantity and quality of DNA to permit genetic analyses (b) and that the source of serum can be archived for many years.

Alleles↗
PubMed1989

Genetic analysis of prototrophic natural variants of Candida albicans.

To facilitate genetic analysis of Candida albicans natural variants, we have isolated a dominant mycophenolic acid-resistant mutant. Mycophenolic acid-resistant auxotrophs were used to analyze prototrophic natural variants by spheroplast fusion. The fusion products were shown to be heterozygous for many of the parental chromosomes by molecular and genetic criteria. Using this approach, we have found that one type of morphologic variation is due to a recessive change and identified three dominant 5-fluorocytosine-resistant mutants. Rare fusion products express recessive parental markers. These exceptional progeny should be useful for linkage analysis and strain construction.

Candida albicans↗
PubMed1995

Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations.

BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.

Adult↗
PubMed2006

Friedreich's ataxia: a clinical and genetic analysis.

We report a patient with genetically confirmed Friedreich's ataxia (FRDA) who developed a previously unreported feature of a mixed sleep apnea. Initial mutation analysis, by PCR, of the parental frataxin alleles showed an apparent de novo mutation in the maternal germline. Further investigation using Southern blot analysis showed that the mother did carry an expanded mutant frataxin allele. Based upon published data, FRDA resulting from at least one allelic spontaneous expansion mutation is rare with a frequency of less than 1/1,000,000. The presence of such a mutation should be confirmed by Southern blot analysis. Our patient expands the neurological features of FRDA to include sleep apnea. The genetic analysis of the family demonstrates the importance of Southern blot analysis for accurate genotyping which, in turn, has implications for genetic counseling.

Adult↗
PubMed1992

The molecular and genetic analysis of mouse development.

This review describes some recent advances in the molecular-genetic analysis of mouse development. Reversed genetics and gene assignment have been used to isolate genes affected in developmental mutations. The establishment of a high-density molecular-genetic map promises to facilitate cloning of additional genes with developmental functions. Based on molecular, biochemical or other biological criteria many mouse genes that code for transcriptional regulators, growth-factor-like molecules and their receptors have been isolated. The role of these genes during development can be analysed in vivo after producing targeted mutations. Mutations can be generated by homologous recombination in the genome of embryonic stem cells and can then be introduced into the mouse germ line by means of germ-line chimaeras. Additional approaches employing stem cells to identify and mutate putative developmental genes are coming into use.

Animals↗
PubMed2003

[Clinical characteristics and genetic analysis of rare chromosome aberration in peripheral blood].

OBJECTIVE: To investigate the main clinical characteristics and genetic analysis of rare chromosome aberration in peripheral blood. METHODS: Peripheral blood cells were cultured for 72 hours with routine method and slids performed, and then the slide was read and mode analysis was carried out. The diagnostic standard of rare chromosomal aberation was: 1-2 abnormal kary types were found in every 30, 60, 200 mitotic phass. RESULTS: The main clinical characteristics of 52 cases of individual chromosomal aberation in peripheral blood included: 1. spontaneous abortion; 2. abnormal sex development; 3. reproduction diseases; and 4. morbid and deformity. CONCLUSION: Rare chromosomal aberation should be regarded as chromosomal diseases. Prenatal diagnosis is necessary for people with such chromosomal aberation in their reproductive actions.

Abortion, Habitual↗
PubMedDate not supplied

Molecular genetic analysis of a small bowel primitive neuroectodermal tumor.

We present a pediatric peripheral primitive neuroectodermal tumor (pPNET) localized exclusively to the small bowel. The tumor presented in an adolescent male and the diagnosis was confirmed by electron microscopy, CD99 immunopositivity, and molecular genetic analysis that demonstrated an EWS-FLI1 type 2 fusion transcript. This case report and a review of the literature underscore the considerable phenotypic overlap in EWS-related tumors in this site and the necessity for molecular genetic analysis to permit accurate classification.

Adolescent↗
PubMed2005

High-performance genetic analysis on microfabricated capillary array electrophoresis plastic chips fabricated by injection molding.

We have developed a novel technique for mass production of microfabricated capillary array electrophoresis (mu-CAE) plastic chips for high-speed, high-throughput genetic analysis. The mu-CAE chips, containing 10 individual separation channels of 50-microm width, 50-microm depth, and a 100-microm lane-to-lane spacing at the detection region and a sacrificial channel network, were fabricated on a poly(methyl methacrylate) substrate by injection molding and then bonded manually using a pressure-sensitive sealing tape within several seconds at room temperature. The conditions for injection molding and bonding were carefully characterized to yield mu-CAE chips with well-defined channel and injection structures. A CCD camera equipped with an image intensifier was used to monitor simultaneously the separation in a 10-channel array with laser-induced fluorescence detection. High-performance electrophoretic separations of phiX174 HaeIII DNA restriction fragments and PCR products related to the human beta-globin gene and SP-B gene (the surfactant protein B) have been demonstrated on mu-CAE plastic chips using a methylcellulose sieving matrix in individual channels. The current work demonstrated greatly simplified the fabrication process as well as a detection scheme for mu-CAE chips and will bring the low-cost mass production and application of mu-CAE plastic chips for genetic analysis.

Chemistry Techniques, Analytical↗
PubMed2004

Genetic analysis of an incomplete bio operon in a biotin auxotrophic strain of Bacillus subtilis natto OK2.

We describe the genetic analysis of the bio operon of the biotin auxotrophic Bacillus subtilis natto OK2 strain. The OK2 strain would only cross-feed with the Escherichia coli bioB mutant and also grew well in medium containing dethiobiotin. Sequencing analysis revealed two significant genetic alterations in the bioW and bioF genes within the bio operon of the OK2 strain. Complementation analysis with B. subtilis 168 bio mutants demonstrated that only the bioB gene could complement, but other bio operon genes could not. A bio(+) transformant, isolated from an OK2 strain, has biotin autotrophy.

Bacillus subtilis↗
PubMed1996

Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A.

OBJECTIVE: Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto-oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations. DESIGN: Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto-oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C-cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24-hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations. PATIENT: Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A. RESULTS: Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto-oncogene analysis identified all these individuals. Mutations of the RET proto-oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests. CONCLUSION: Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.

Base Sequence↗
PubMed1987

Isozymes as bioprobes for genetic analysis of nonhuman primates.

The identification and the utilization of genetically determined electrophoretic differences of enzymes between the individuals of species as well as between cell lines have played an important role in the advancement of mammalian genetics during the past quarter of a century. In an explicit search we found a number of red cell enzyme polymorphisms in each of the following four species: chimpanzees, orang utans, rhesus monkeys and brown capuchins. Allelic distribution patterns among populations have indicated trends of subspeciation among chimpanzees and orang utans due to geographic barriers leading to reproductive isolation. Investigations of quantitative levels of red cell glucose-6-phosphate dehydrogenase have suggested that relative activity profiles of certain enzymes among species may be helpful in studies of the evolution of physiological traits and their biological significance during speciation. A large number of biochemical genetic markers in primate-rodent (i.e., chimpanzee-, gorilla-, orang utan-, rhesus monkey- and African green monkey-Chinese hamster) somatic cell hybrids have been identified and are useful for primate genetic analysis. Some of the biologically relevant observations on the enzyme markers in the above mentioned primate species are discussed.

Animals↗
PubMed2003

Genetic analysis of familial colorectal cancer in Israeli Arabs.

Colorectal cancers (CRC) among Israeli Arabs differ from those diagnosed in Jewish Israeli individuals in two manners: an earlier age of occurrence and a low frequency. These differences are unaccounted for and thus prompted us to perform genetic analysis in Israeli Arab CRC patients. Analysis included the major Hereditary non-polyposis colorectal cancer (HNPCC) genes and the APC I1307K mutation (MIM# 175100.0029). Twenty-five patients and 25 relatives from 24 unrelated families were clinically classified according to personal and familial cancer history. If MSI (microsatellite instability) was displayed in tumor tissue, patients underwent mutation analysis of the MSH2 and MLH1 genes using DGGE (denaturing gradient gel electrophoresis) and sequencing. MSI was detected in 9/21 of the tumors tested (43%). Two novel missense mutations were diagnosed among 11 fully analyzed patients: a change of A to G at position 380 in MSH2 (N127S), and a D601G mutation in MLH1. The I1307K mutation was detected in 8 families (8/24, 33.3%). This is the first report of genetic analysis in familial CRC associated genes among Israeli Arabs. We suggest that the I1307K mutation may contribute to CRC in Israeli Arabs and that inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC.

Adaptor Proteins, Signal Transducing↗
PubMed1989

[Genetic analysis and simulation of the virulence of Yersinia pestis].

The genetic analysis of Y. pestis virulence factors accomplished in the 358 strain isogenic system allowed us to determine a minimal set of known factors providing pathogenicity. The combination of chromosomal marker Pgm+ and calcium dependence plasmid (pCad) is shown to be sufficient for preserving the virulence of Y. pestis. Experimental modelling of virulence in this microorganism by the genetic exchange methods was carried out. The reduced virulence of the strains Pgm+ and pCad+ for guinea pigs was detected.

Animals↗
PubMed1999

Genetic analysis of leishmania parasites in Ecuador: are Leishmania (Viannia) panamensis and Leishmania (V.) Guyanensis distinct taxa?

In the course of an epidemiologic survey in Ecuador, the following collection of Leishmania stocks was isolated: 28 from patients with clinical signs of leishmaniasis, 2 from sloths, 1 from a dog, and 4 from sand flies. For genetic characterization of these stocks, multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD) were used. Twenty six of the 35 stocks were identified as either Leishmania (V.) panamensis or L. (V.) guyanensis, 2 stocks were identified as L. (V.) braziliensis, the 2 stocks from sloths showed specific genotypes, and 5 stocks were characterized as hybrids between L. (V.) braziliensis and L. (V.) guyanensis. These data show that genetic diversity of Leishmania in Ecuador is high and that L. (V.) panamensis/guyanensis is the dominant group in this country. The genetic analysis questioned the distinctness between the two species L.(V.) panamensis and L. (V.) guyanensis, since MLEE and RAPD data did not indicate that L. (V.) panamensis and L. (V.) guyanensis correspond to distinct monophyletic lines. Population genetic analysis performed on the L. (V.) panamensis/guyanensis group favors the hypothesis of a basically clonal population structure.

Animals↗
PubMed2003

TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism.

The prevalence of thyroid diseases in children with Down's syndrome (DS) is about 3%. The most frequently observed condition is autoimmune subclinical hypothyroidism (SH). Autoimmune SH must be distinguished from defects in the biological activity of the TSH molecule or from the rare inherited condition of thyroid resistance to TSH. To investigate this last aspect we studied 12 patients with DS that had moderately elevated TSH with normal free thyroid hormones without signs of autoimmunity. For the genetic analysis the genomic DNA was extracted from peripheral lymphocytes. All the exons of the TSH receptor (TSHr) and Gs(alpha) genes were sequenced. The genetic analysis of the TSHr gene revealed the presence of four polymorphic variants. In two patients there was an allelic variant in the exon 1 (Pro52Thr--in one patient in the heterozygous state and in the other as a homozygous substitution). In one patient there was an allelic variant in the exon 1 (Asp36His) in the heterozygous state. In 11 patients there was a silent polymorphism in the exon 7 at nucleotide 561. All patients were homozygous for a silent polymorphism in the exon 9 at nucleotide 855. No inactivating mutations of TSHr or Gs(alpha) genes were identified in the 12 patients. In conclusion, our results seem to exclude the role of TSHr or Gs(alpha) gene mutations in the pathogenesis of the non-autoimmune SH observed in some children with DS.

Adolescent↗
PubMed1980

[Genetic analysis of the structure of relations between certain physiologic traits. II. Analysis of glucose tolerance indices and plasma cholesterol levels].

A genetic analysis of the characteristics of sugar curve (138 pairs) and cholesterol levels (CS) in the plasma (283) was carried out on a twin sample of 18-40 years old, taken from the Twin Register. Estimation of heritability were 0.66 for the sugar level in the blood before taking breakfast (S0), 0.5 for the sugar level 1 hour after taking 50 g of glucose (S1); 0.43 for the sugar level 2 hours after taking glucose (S2), and 0.38 for CS. There were genetic correlations between all the four characteristics, and they were 0.7 for S0-S1; 0.12 for S1-S2; 0.6 for S0-S2. Genetic correlation between the characteristics of sugar curve and the CS levels were 0.28 for CS-S0; 0.38 for CS-S1; 0.26 for CS-S2.

Adolescent↗