Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Genetic Variation: Genotypic differences observed among individuals in a population.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Genetics, Population: The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.HLA-DQ beta-Chains: Transmembrane proteins that form the beta subunits of the HLA-DQ antigens.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.HLA-DRB1 Chains: A subtype of HLA-DRB beta chains that includes over one hundred allele variants. The HLA-DRB1 subtype is associated with several of the HLA-DR SEROLOGICAL SUBTYPES.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.Geography: The science dealing with the earth and its life, especially the description of land, sea, and air and the distribution of plant and animal life, including humanity and human industries with reference to the mutual relations of these elements. (From Webster, 3d ed)Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.HLA-DQ alpha-Chains: Transmembrane proteins that form the alpha subunits of the HLA-DQ antigens.Phylogeography: A field of study concerned with the principles and processes governing the geographic distributions of genealogical lineages, especially those within and among closely related species. (Avise, J.C., Phylogeography: The History and Formation of Species. Harvard University Press, 2000)Y Chromosome: The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained.Homozygote: An individual in which both alleles at a given locus are identical.HLA-DR3 Antigen: An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*03 alleles.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Genes, MHC Class II: Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and in the I region in mice.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.Genealogy and HeraldryHeterozygote: An individual having different alleles at one or more loci regarding a specific character.DNA, Chloroplast: Deoxyribonucleic acid that makes up the genetic material of CHLOROPLASTS.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Cytochromes b: Cytochromes of the b group that have alpha-band absorption of 563-564 nm. They occur as subunits in MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III.Chromosomes, Human, Y: The human male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans.Bahrain: An independent state, an archipelago in the western Persian Gulf, northwest of Qatar. It comprises low-lying islands of Bahrain (the largest), Muharraq, Sitra, and several islets. It has extensive oil fields. The name comes from the Arabic al-bahrayn, "the two seas", with reference to its lying in the middle of a bay with its "two seas" east and west of it. (From Webster's New Geographical Dictionary, 1988, p107 & Room, Brewer's Dictionary of Names, 1992, p45)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.China: A country spanning from central Asia to the Pacific Ocean.African Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Africa.HLA-B8 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*08 allele family.AfricaHLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.Gene Pool: The total genetic information possessed by the reproductive members of a POPULATION of sexually reproducing organisms.Polynesia: The collective name for the islands of the central Pacific Ocean, including the Austral Islands, Cook Islands, Easter Island, HAWAII; NEW ZEALAND; Phoenix Islands, PITCAIRN ISLAND; SAMOA; TONGA; Tuamotu Archipelago, Wake Island, and Wallis and Futuna Islands. Polynesians are of the Caucasoid race, but many are of mixed origin. Polynesia is from the Greek poly, many + nesos, island, with reference to the many islands in the group. (From Webster's New Geographical Dictionary, 1988, p966 & Room, Brewer's Dictionary of Names, 1992, p426)EuropeLikelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters.Genes, MHC Class I: Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), DLA (dog), GPLA (guinea pig), H-2 (mouse), RT-1 (rat), HLA-A, -B, and -C class I genes of man.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Genetic Loci: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Gene Flow: The change in gene frequency in a population due to migration of gametes or individuals (ANIMAL MIGRATION) across population barriers. In contrast, in GENETIC DRIFT the cause of gene frequency changes are not a result of population or gamete movement.HLA-A1 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*01 allele family.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships.Indians, South American: Individual members of South American ethnic groups with historic ancestral origins in Asia.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Quantitative Trait Loci: Genetic loci associated with a QUANTITATIVE TRAIT.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Wolves: Any of several large carnivorous mammals of the family CANIDAE that usually hunt in packs.South AmericaAsia: The largest of the continents. It was known to the Romans more specifically as what we know today as Asia Minor. The name comes from at least two possible sources: from the Assyrian asu (to rise) or from the Sanskrit usa (dawn), both with reference to its being the land of the rising sun, i.e., eastern as opposed to Europe, to the west. (From Webster's New Geographical Dictionary, 1988, p82 & Room, Brewer's Dictionary of Names, 1992, p34)Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.HLA-C Antigens: Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).H-2 Antigens: The major group of transplantation antigens in the mouse.DNA, Plant: Deoxyribonucleic acid that makes up the genetic material of plants.Receptors, KIR: A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).Siberia: A region, north-central Asia, largely in Russia. It extends from the Ural Mountains to the Pacific Ocean and from the Arctic Ocean to central Kazakhstan and the borders of China and Mongolia.Inheritance Patterns: The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.Nuclear Family: A family composed of spouses and their children.Steroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).JapanHaploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented once. Symbol: N.Histocompatibility Testing: Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.

Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover. (1/12035)

OBJECTIVE: To examine the relationship between a common polymorphism within intron 1 of the COL1A1 gene and osteoporosis in a nested case-control study. METHODS: We studied 185 healthy women (mean +/- SD age 54.3+/-4.6 years). Bone mineral density (BMD) was measured using dual x-ray absorptiometry, and fractures were determined radiographically. The COL1A1 genotype was assessed using the polymerase chain reaction and Bal I endonuclease digestion. RESULTS: Genotype frequencies were similar to those previously observed and in Hardy-Weinberg equilibrium: SS 61.1%, Ss 36.2%, and ss 2.7%. Carriage of at least one copy of the "s" allele was associated with a significant reduction in lumbar spine BMD (P = 0.02) and an increased risk of total fracture (P = 0.04). Urinary pyridinoline levels were significantly elevated in those with the risk allele (P < 0.05). CONCLUSION: These data support the findings that the COL1A1 gene polymorphism is associated with low BMD and fracture risk, and suggest a possible physiologic effect on total body turnover of type I collagen.  (+info)

A novel method for determining linkage between DNA sequences: hybridization to paired probe arrays. (2/12035)

Cooperative hybridization has been used to establish physical linkage between two loci on a DNA strand. Linkage was detected by hybridization to a new type of high-density oligonucleotide array. Each synthesis location on the array contains a mixture of two different probe sequences. Each of the two probes can hybridize independently to a different target sequence, but if the two target sequences are physically linked there is a cooperative increase in hybridization yield. The ability to create and control non-linear effects raises a host of possibilities for applications of oligonucleotide array hybridization. The method has been used to assign linkage in 50:50 mixtures of DNA containing single nucleotide polymorphisms (SNPs) separated by 17, 693, 1350 and 2038 bp and to reconstruct haplotypes. Other potential uses include increasing the specificity of hybridization in mutation detection and gene expression monitoring applications, determining SNP haplotypes, characterizing repetitive sequences, such as short tandem repeats, and aiding contig assembly in sequen-cing by hybridization.  (+info)

The haplotype distribution of two genes of citrus tristeza virus is altered after host change or aphid transmission. (3/12035)

Genetic variability of citrus tristeza virus (CTV) was studied using the haplotypes detected by single-strand conformation polymorphism (SSCP) analysis of genes p18 and p20 in six virus populations of two origins. The Spanish group included a CTV isolate and subisolates obtained by graft-transmission to different host species. The other included two subisolates aphid-transmitted from a single Japanese isolate. The homozygosity observed for gene p20 was always significantly higher than that expected under neutral evolution, whereas only three populations showed high homozygosity for p18, suggesting stronger host constraints for p20 than for p18. Sequential transmissions of a Spanish isolate to new host species increased the difference between its population and that of the successive subisolates for gene p18, as estimated by the F statistic. Analysis of molecular variance indicated that variation between both groups of populations was not statistically significant, whereas variations between populations of the same group or within populations were significant for both genes studied. Our data indicate that selection affects the haplotype distribution and that adaptation to a new host can be as important or more as the geographical origin. Variation of the CTV populations after host change or aphid transmission may explain in part the wide biological variability observed among CTV isolates.  (+info)

DYT1 mutation in French families with idiopathic torsion dystonia. (4/12035)

A GAG deletion at position 946 in DYT1, one of the genes responsible for autosomal dominant idiopathic torsion dystonia (ITD), has recently been identified. We tested 24 families and six isolated cases with ITD and found 14 individuals from six French families who carried this mutation, indicating that 20% of the affected families carried the DYT1 mutation. Age at onset was always before 20 years (mean, 9+/-4 years). Interestingly, the site of onset was the upper limb in all but one patient. Dystonia was generalized in seven patients and remained focal or segmental in three patients. The absence of common haplotypes among DYT1 families suggests that at least six independent founder mutations have occurred. In addition, one Ashkenazi Jewish family carried the common haplotype described previously in Ashkenazi Jewish patients, but it was absent in the other family. Moreover, the dystonia remained focal in the latter family when compared with the usual generalized phenotype in patients with the common Ashkenazi Jewish haplotype. This indicates that there are at least two founder mutations in this population.  (+info)

A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer. (5/12035)

The frequency, origin, and phenotypic expression of a germline MSH2 gene mutation previously identified in seven kindreds with hereditary non-polyposis cancer syndrome (HNPCC) was investigated. The mutation (A-->T at nt943+3) disrupts the 3' splice site of exon 5 leading to the deletion of this exon from MSH2 mRNA and represents the only frequent MSH2 mutation so far reported. Although this mutation was initially detected in four of 33 colorectal cancer families analysed from eastern England, more extensive analysis has reduced the frequency to four of 52 (8%) English HNPCC kindreds analysed. In contrast, the MSH2 mutation was identified in 10 of 20 (50%) separately identified colorectal families from Newfoundland. To investigate the origin of this mutation in colorectal cancer families from England (n=4), Newfoundland (n=10), and the United States (n=3), haplotype analysis using microsatellite markers linked to MSH2 was performed. Within the English and US families there was little evidence for a recent common origin of the MSH2 splice site mutation in most families. In contrast, a common haplotype was identified at the two flanking markers (CA5 and D2S288) in eight of the Newfoundland families. These findings suggested a founder effect within Newfoundland similar to that reported by others for two MLH1 mutations in Finnish HNPCC families. We calculated age related risks of all, colorectal, endometrial, and ovarian cancers in nt943+3 A-->T MSH2 mutation carriers (n=76) for all patients and for men and women separately. For both sexes combined, the penetrances at age 60 years for all cancers and for colorectal cancer were 0.86 and 0.57, respectively. The risk of colorectal cancer was significantly higher (p<0.01) in males than females (0.63 v 0.30 and 0.84 v 0.44 at ages 50 and 60 years, respectively). For females there was a high risk of endometrial cancer (0.5 at age 60 years) and premenopausal ovarian cancer (0.2 at 50 years). These intersex differences in colorectal cancer risks have implications for screening programmes and for attempts to identify colorectal cancer susceptibility modifiers.  (+info)

Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1-2 polymorphism and contribution to founder effect. (6/12035)

Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with autosomal dominant inheritance. The gene responsible was recently cloned and this disorder was found to be the result of a CAG expansion in its open reading frame. We analysed 13 SCA2 patients in seven unrelated families in Gunma Prefecture, Japan. In four of the seven families, we detected CCG or CCGCCG interruptions in only the expanded alleles. Cosegregation of these polymorphisms with SCA2 patients was established within each family. Together with the results of haplotype analyses, we considered that at least two founders were present in our area and that these (CCG)1-2 polymorphisms may make analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expanded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single CAG. Moreover, the presence of these polymorphisms may lead to miscounting the repeat size by conventional estimation using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by sequencing.  (+info)

Der(22) syndrome and velo-cardio-facial syndrome/DiGeorge syndrome share a 1.5-Mb region of overlap on chromosome 22q11. (7/12035)

Derivative 22 (der[22]) syndrome is a rare disorder associated with multiple congenital anomalies, including profound mental retardation, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional t(11;22)(q23;q11) translocation, owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. The trisomic region on chromosome 22 overlaps the region hemizygously deleted in another congenital anomaly disorder, velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). Most patients with VCFS/DGS have a similar 3-Mb deletion, whereas some have a nested distal deletion endpoint resulting in a 1.5-Mb deletion, and a few rare patients have unique deletions. To define the interval on 22q11 containing the t(11;22) breakpoint, haplotype analysis and FISH mapping were performed for five patients with der(22) syndrome. Analysis of all the patients was consistent with 3:1 meiotic malsegregation in the t(11;22) carrier parent. FISH-mapping studies showed that the t(11;22) breakpoint occurred in the same interval as the 1.5-Mb distal deletion breakpoint for VCFS. The deletion breakpoint of one VCFS patient with an unbalanced t(18;22) translocation also occurred in the same region. Hamster-human somatic hybrid cell lines from a patient with der(22) syndrome and a patient with VCFS showed that the breakpoints occurred in an interval containing low-copy repeats, distal to RANBP1 and proximal to ZNF74. The presence of low-copy repetitive sequences may confer susceptibility to chromosome rearrangements. A 1.5-Mb region of overlap on 22q11 in both syndromes suggests the presence of dosage-dependent genes in this interval.  (+info)

Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11. (8/12035)

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogeneous form of early-onset familial spastic ataxia with prominent myelinated retinal nerve fibers. More than 300 patients have been identified, and most of their families originated in the Charlevoix-Saguenay region of northeastern Quebec, where the carrier prevalence has been estimated to be 1/22. Consistent with the hypothesis of a founder effect, we observed excess shared homozygosity at 13q11, among patients in a genomewide scan of 12 families. Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation. On the basis of haplotypes composed of seven marker loci that spanned 11.1 cM, the most likely position of the ARSACS locus was 0.42 cM distal to the SGCG polymorphism. Two groups of ARSACS-associated haplotypes were identified: a large group that carries a common SGCG allele and a small group that carries a rare SGCG allele. The haplotype groups do not appear to be closely related. Therefore, although chromosomes within each haplotype group may harbor a single ARSACS mutation identical by descent, the two mutations could have independent origins.  (+info)

  • Because (1) the majority of the haplotypes are population specific and (2) the patterns of linkage disequilibrium, recombination, and haplotype diversity are markedly different between gene regions, these data show the importance of either ethnically matched controls or within-family-based disease-gene association studies. (unthsc.edu)
  • Because haplotypes are highly likely to be preserved in populations, there are several algorithms for attempting to conduct pseudo-phasing on large number of unrelated people. (snpedia.com)
  • This can lead to over-estimation of the risk by including odds ratio of different SNP's along same haplotype, or flip-flop phenomenon where the effect of the SNP is opposite in different populations due to population-dependent variation in the haplotype. (snpedia.com)
  • Single nucleotide polymorphism (SNP) haplotypes can be determined without ambiguity when an individual does not have more than one heterozygous site in a given genomic region. (fujita-hu.ac.jp)
  • A number of packages provide haplotype estimation for unrelated individuals with ambiguous haplotypes (due to unknown linkage phase) and allow testing for associations between the estimated haplotypes and phenotypes (including co-variates) under a GLM framework. (unipd.it)
  • Haplotypes have also important applications in genetic genealogy and determining identity by descent . (snpedia.com)
  • Unless, of course, another Carlow Nolan lineage emerges through future Y-DNA testing and the results prove a closer genetic match to the Northwest Irish (Niall of the Nine Hostages) R1b1c7 haplotype. (worldfamilies.net)
  • For family data, tdthap offers an implementation of the Transmission/Disequilibrium Test (TDT) for extended marker haplotypes. (unipd.it)
  • Unfortunately, most sequencing platforms are inherently inadequate with respect to resolving haplotype information beyond several hundred base pairs due to limitations on read length [ 14 ], and existing assembly algorithms for haplotype reconstruction from quasispecies suffer from poor sensitivity and specificity [ 15 ]. (biomedcentral.com)
  • All relevant current issues in computational methods for SNP and haplotype analysis and their applications to disease associations are addressed. (springer.com)
  • Nolan Lineage III matches the Northwest Irish (Niall of the Nine Hostages) 25-marker haplotype exactly to the 22nd marker mismatching at DYS #464b and 464c making the mismatch two points among the 25-markers compared. (worldfamilies.net)
  • Next Gen Sequencing can thus provide not only perfectly phased genome, but also a haplotype map which can be used to impute untested SNP's from nearby known ones. (snpedia.com)
  • Haplotypes are important for example because many of the SNP's found by genome-wide association studies aren't the true cause but simply occur on same haplotype and are thus inherited together. (snpedia.com)
  • However, any meaningful attempt to study intra-quasispecies interactions will require the ability to determine viral haplotypes (here, 'haplotype' refers to the set of SNVs that occur on a particular copy of the viral genome) so that the correlation and co-occurrence of SNVs within quasispecies can be characterized. (biomedcentral.com)
  • Applying BAsE-Seq to a clinical sample, we obtained over 9,000 viral haplotypes, which provided an unprecedented view of hepatitis B virus population structure during chronic infection. (biomedcentral.com)
  • The cosegregating haplotype was seen in all (6/6) samples of Ashkenazi descent, whereas in the general population it has a low frequency (0.02) and was not found in African Americans. (unthsc.edu)
  • We present a method for obtaining long haplotypes, of over 3 kb in length, using a short-read sequencer, Barcode-directed Assembly for Extra-long Sequences (BAsE-Seq). (biomedcentral.com)
  • An organism's genotype may not define its haplotype uniquely. (wikipedia.org)
  • The haplotype resolution from xor-genotype data has been recently formulated as a new model for genetic studies . (psu.edu)
  • 2002). Given a meiotic model for the combination of a pair of haplotypes into a genotype during mating, and given a set of observed genotypes in a sample from a human population, it is of great interest to identify the underlying haplotypes (Stephens et al. (psu.edu)
  • These data also indicate that the risk associated with specific HLA haplotypes can be influenced by the genotype context and that the trans- complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk. (diabetesjournals.org)
  • Hence genotype (blended) SNP data will be collected, and the desired haplotype (partitioned) data must then be (partially) inferred. (biomedsearch.com)
  • These haplotypes can be used to guide genotype imputation and haplotype estimation. (ashg.org)
  • 5%. I will describe our evaluation of strategies for merging haplotypes and variant lists across studies and advances in methods for genotype likelihood-based haplotype estimation that can be applied to 10,000s of samples. (ashg.org)
  • The majority of haplotypes will also be deposited in the European Genotype Archive. (ashg.org)
  • Instead of providing a separate complete chromosome sequence for each haplotype, which could cause confusion with divergent chromosome coordinates and ambiguity about which sequence is the official reference, the Genome Reference Consortium (GRC) adds alternate locus sequences, ranging from tens of thousands of bases up to low millions of bases in size, to represent the distinct haplotypes. (ucsc.edu)
  • Second, if there are multiple solutions, can we find one that is most parsimonious in terms of the number of distinct haplotypes.We give reductions that suggests that the answer to both questions is "no. (umd.edu)
  • For the second problem of computing a PPH solution that minimizes the number of distinct haplotypes, we show that the problem is NP-hard using a reduction from Vertex Cover (Garey and Johnson, 1979). (umd.edu)
  • The biological key to that strategy is the surprising fact that genomic DNA can be partitioned into long blocks where genetic recombination has been rare, leading to strikingly fewer distinct haplotypes in the population than previously expected [12, 6, 21, (psu.edu)
  • Recently, Gusfield introduced the perfect phylogeny haplotyping problem, as an algorithmic implication of the no-recombination in long blocks observation, together with the standard population-genetic assumption of infinite sites. (umd.edu)
  • The next high-priority phase of human genomics will involve the development of a full Haplotype Map of the human genome . (psu.edu)
  • Background: Haplotype phasing is an important problem in the analysis of genomics information. (inria.fr)
  • Haplotype networks are graphs in which a subset of vertices is labelled, used in comparative genomics as an alternative to trees. (archives-ouvertes.fr)
  • Current genomics techniques enabled genome-wide identification of these Asian introgressed haplotypes in modern European pig breeds.We propose that the Asian variants are still present because they affect phenotypes thatwere important for ancient traditional, as well as recent, commercial pig breeding. (wur.nl)
  • A haplogroup is a group of similar haplotypes that share a common ancestor with a single-nucleotide polymorphism mutation. (wikipedia.org)
  • In this paper, we build a novel and integrated statistical framework for multilocus haplotype reconstruction in a full-sib tetraploid family from biallelic marker dosage data collected from single-nucleotide polymorphism (SNP) arrays or next-generation sequencing technology given a genetic linkage map. (wur.nl)
  • Four of these differed from Japanese haplotypes by one single nucleotide polymorphism (SNP), possibly indicating a recent in situ change. (springer.com)
  • Haplotype data provide an alternative method for detecting associations between variants in weak linkage disequilibrium with genotyped variants and a given trait of interest. (nature.com)
  • Using such haplotypes to highlight regions for sequencing may lead to the identification of the underlying causal variants. (nature.com)
  • 31,500 sequenced whole genomes, aggregated over 20 studies of predominantly European ancestry, to create a very large reference panel of human haplotypes where ~50M genetic variants are observed 5 or more times. (ashg.org)
  • Our full resource is available to the community through imputation servers that enable scientists to impute missing variants in any study and respect the privacy of subjects contributing to the studies that constitute the Haplotype Reference Consortium. (ashg.org)
  • While the read length of the single-molecule protocols is long, the relatively high error rate limits the ability to accurately detect the genetic variants and assemble them into the haplotype-specific isoforms. (embs.org)
  • The advantage of the SNP1 approach is that determining the linkage phase of the haplotypes is not required and the markers do not need to be mapped. (genetics.org)
  • The approach is identical to the exploitation of haplotype blocks (regions of complete or almost complete linkage disequilibrium) in the human genome for association mapping ( 9 ) but requires a different analysis to take advantage of the small number of founder animals from which laboratory strains are descended. (pnas.org)
  • We divide haplotype reconstruction into two stages: parental linkage phasing for reconstructing the most probable parental haplotypes and ancestral inference for probabilistically reconstructing the offspring haplotypes conditional on the reconstructed parental haplotypes. (wur.nl)
  • Morton, Newton E(Dec 2007) Blocks of Limited Haplotype Diversity. (els.net)
  • Correlations between surname rank and degree of diversity exist: the more common the surname, the greater the diversity of Y-chromosomal haplotypes associated with the name. (bl.uk)
  • A team from the Plant Pathology department at the US University has developed the extensive wheat diversity map - a haplotype map - of 62 varieties from across the world. (bakeryandsnacks.com)
  • We suggest that an alternative haplotype designated as aHt maybe alternative to minHt in respect of its Y-STR content with the highest gene diversity value. (scirp.org)
  • This allows partitioning the reads into two parental haplotypes. (embs.org)
  • and it has not been found in any other human population sampled so far (out of a total of more than 10 000 mtDNA haplotypes for this sequence held in the GenBank sequence repository), except the Castle Mall individual reported on here. (royalsocietypublishing.org)
  • Although polyoma virus middle T-driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. (aacrjournals.org)
  • However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals. (wikipedia.org)
  • An alternative explanation may be that the particular haplotype may have been associated with the movement of the Phrygians into Asia Minor. (blogspot.com)
  • The term 'haplogroup' refers to the SNP/unique-event polymorphism (UEP) mutations that represent the clade to which a collection of particular human haplotypes belong. (wikipedia.org)
  • Haplotype information is relevant to gene regulation, epigenetics, genome-wide association studies, evolutionary and population studies, and the study of mutations. (inria.fr)
  • Analysis of further MPL -positive, V617F-negative cases confirmed an excess of 46/1 (n = 176, P = .002), but no association between MPL mutations and MPL haplotype was seen. (bloodjournal.org)
  • Patients with different haplotypes are assumed to be unrelated and thus to carry independent mutations. (lu.se)
  • All but one of thc 13 mutations occur in at least 2 haplotypes thus. (lu.se)
  • All but one of thc 13 mutations occur in at least 2 haplotypes thus pinpointing 12 mutational hotspots and mutations that can be clearly considered detrimental. (lu.se)
  • An ancestral 5′ recombination event in the chromosomal region between intron 5 and exon 8 has been advocated to explain the origin of haplotype C, which resembles haplotype A at the polymorphic sites in the 5′ region of the gene and resembles the B haplotype in the 3′ region ( 5 ). (diabetesjournals.org)
  • STRASBURG, PA- A natural history study has provided the first comprehensive clinical description of spinal muscular atrophy (SMA) within the Amish and Mennonite communities and correlates ancestral chromosome 5 haplotypes and SMN2 copy number with disease severity. (clinicforspecialchildren.org)
  • We then apply a novel HMM method (duoHMM) to combine the SHAPEIT2 haplotypes with any family information to infer the inheritance pattern of each meiosis at all sites across each chromosome. (plos.org)
  • We infer that VDR haplotypes might influence the risk of HIV-1 acquisition. (ebscohost.com)
  • HaploRec [1,is a statistical haplotype reconstruction algorithm targeted for large-scale disease association studies. (helsinki.fi)
  • Haplotype estimation is a key first step of many disease and population genetic studies. (plos.org)
  • This project investigates the effect of (i) SLE-associated MHC haplotypes, and (ii) IFN-α stimulation on gene regulation in ex vivo B cells, in order to further our understanding of how these factors contribute to disease risk. (bl.uk)
  • These results suggest a regulatory role for disease-associated MHC haplotypes, and implicate BTN3A2 as a novel candidate gene on the DRB1*03:01 haplotype. (bl.uk)
  • The Bantu haplotype has been associated with higher disease severity and high incidence of organ, damage while the Benin haplotype is associated with an intermediate clinical course. (scielo.br)
  • Haplotypes of the fibrinogen gene and cerebral small vessel disease. (bmj.com)
  • 2.0 (June 2005) This version introduced an EM-based algorithm and a segmentation-based haplotype probability model, and featured several computational improvements, allowing the use of larger data sets. (helsinki.fi)
  • A polynomial-time exact algorithm for haplotype reconstruction without recombinants is also presented. (nih.gov)
  • Bansal, V., Bafna, V.: HapCUT: an efficient and accurate algorithm for the haplotype assembly problem. (springer.com)
  • Because complete exploration of all possible solutions for constructing haplotypes is computationally prohibitive, our approach uses a greedy algorithm based on windows of fixed sizes. (diva-portal.org)
  • The haplotype is converted to number , considering the first variation as zero and the alternate value as 1 (see expanded description below). (ubuntu.com)
  • These two breakpoints are thought to flank the gene interval that harbors most of the genetic variation that determines ACE activity, with haplotypes B, C, and D having higher ACE activity than haplotype A ( 6 ). (diabetesjournals.org)
  • Clear favorable haplotypes, contributing 40-60% of the variation for PHS tolerance, were identified for QTL 3A and 4A. (frontiersin.org)
  • predicts total breeding values on the basis of a large number of marker haplotypes across the entire genome. (genetics.org)
  • Sun X, Stephens JC and Zhao H (2004) The impact of sample size and marker selection on the study of haplotype structures. (els.net)
  • Using 800 bp of the non-coding chloroplast marker accD-rbcL, we compared 21 Japanese haplotypes with 46 US samples from 11 states, 2 Canadian samples, and 6 European samples from 4 countries, in order to investigate if there were repeated introductions from Asia. (springer.com)
  • 7 , 8 , 11 First, 46/1 may be inherently more genetically unstable, acquiring V617F at a faster rate than other haplotypes (hypermutability hypothesis). (bloodjournal.org)
  • Second, V617F may arise on all haplotypes at equal rates, but 46/1 may carry an additional factor that either gives a selective advantage to the V617F-positive clone or interacts in some way to increase the likelihood of abnormal blood counts (fertile ground hypothesis). (bloodjournal.org)
  • Clade here refers to a set of haplotypes sharing a common ancestor. (wikipedia.org)
  • SNP1 and SNP2 do not make a distinction between haplotypes that are alike-in-state (AIS) due to a common ancestor ( i.e . (genetics.org)
  • Zhang K, Calabrese P, Nordborg M and Sun F (2002) Haplotype block structure and its applications to association studies: power and study designs. (els.net)
  • Haplotypes are important for example because many of the SNP's found by genome-wide association studies aren't the true cause but simply occur on same haplotype and are thus inherited together. (snpedia.com)
  • Haplotype 2 (G-A-T-A-G-T-G) was associated with presence of silent brain infarcts when compared to the most frequent haplotype (G-G-T-G-G-T-A) (odds ratio (OR) 1.41, 95% CI 1.03-1.94). (bmj.com)
  • 1 , 2 SCA is characterized by a variable clinical course and differences in response to medication, reflecting its complex pathophysiology and suggesting that it can be affected by modulator factors such as the haplotypes of the beta globin chain or fetal hemoglobin (Hb F) levels. (scielo.br)
  • We examined the association of fibrinogen levels and haplotypes with silent brain infarcts and white matter lesions by means of logistic regression models. (bmj.com)