bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic polymorphism of human deoxyribonuclease II (DNase II): low activity levels in urine and leukocytes are due to an autosomal recessive allele
Authors: YASUDA T. , NADANO D. , SAWAZAKI K. , KISHI K. 
Published: September 2007

SummaryThe objectives of this study were to elucidate the genetic basis of human deoxyribonuclease II (DNase II) and to evaluate its usefulness as a genetic and/or diagnostic marker. We have devised a novel, specific and highly sensitive assay method for the urinary and leukocytic enzymes (Yasuda et al. 1991). The distribution of the activities of both enzymes displayed clear‐cut bimodality and the Japanese study population could be classified into two distinct types, namely low‐activity (DNASE2 L) and high‐activity (DNASE2 H), which indicates the existence of a genetic polymorphism in the activity levels of urinary and leukocytic DNase Us. Close correlations between the leukocytic and urinary enzyme activity levels from the same individuals were observed and the types in the leukocyte samples agreed with the types found in the corresponding urine samples. In a population study of 528 unrelated Japanese individuals, the gene frequencies of the low activity (DNASE2*L) and the high activity (DNASE2*H) alleles were calculated to be 0·632 and 0·368, respectively. The sex and age of individuals did not affect the distribution of DNase II activity levels. The family study results were compatible with the model that the low activity type is due to an autosomal recessive gene, which indicates that DNASE2 L represents homozygosity for DNASE2*L and DNASE2 H corresponds to homozygosity for DNASE2*H and heterozygosity for DNASE2*L and DNASE2*H.
Genetic relationship between the 3‘‐VNTR and diallelic apolipoprotein B gene polymorphisms: Haplotype analysis in individuals of European and South Asian origin
Authors: RENGES H‐H. , PEACOCK K. , DUNNING A. M. , TALMUD P. , HUMPHRIES S. E. 
Published: September 2007

SummaryThe genetic relationship amongst apolipoprotein B (apo B) gene polymorphisms (signal peptide insertion/deletion (Leu‐Ala‐Leu‐16/‐14), XbaI (Thr2488), EcoRI (Glu4154→ Lys), Asn4311→ Ser, 3′ ‐VNTR) has been investigated in samples of South Asian (Indian) and Swedish individuals. The frequency distribution of alleles at all these sites was found to be significantly different between the South Asian and the Swedish samples (deletion allele: 0·20 v. 0·31, X + (presence of XbaI cutting site): 0·29 v. 0·55, R‐ (absence of EcoRI cutting site): 0·11 v. 0·19, Ser4311: 0·45 v. 0·19). The distribution of allele frequencies at the VNTR site was bimodal in both populations. However, in South Asians, the most common allele was a 35 repeat unit allele, whilst in the Swedish sample, and in all other reports from Caucasian samples the 37 repeat unit allele was the most frequent (South Asian v. Swedish: 35 allele: 0·36 v. 0·19, 37 allele: 0·25 v. 0·48). Furthermore, four new alleles at the apo B gene 3′ ‐VNTR site (15, 17, 32, 38 repeat unit alleles) were observed in South Asians, of which two (15 and 17 repeat unit alleles) were well outside the bimodal distribution. In both samples, strong linkage disequilibrium and allelic association were detected between alleles at the 3′ ‐VNTR and each of the other sites, and also between the ins/del and XbaI sites and between the XbaI and Asn4311→ Ser sites. The same five common haplotypes as defined by ins/del, XbaI, EcoRI and Asn4311→ Ser were found to be present in both samples comprising 97 and 99 % of the haplotypes observed in the South Asian and Swedish samples respectively. Detailed analysis revealed the predominant occurrence of certain 3′ ‐VNTR alleles on specific haplotypes and demonstrates the usefulness of the VNTR site for haplotyping and representative association studies. A model for the evolutionary relationship of the major haplotypes including the 3′ ‐VNTR site is presented. These findings support a mechanism of replication slippage as a major factor for the generation of new alleles at the apo B 3′ ‐VNTR locus rather than unequal crossing over.
Kinetic properties of the common electrophoretic variants of human S‐adenosylhomocysteine hydrolase (AHCY): the effect of four nucleoside analogue inhibitors
Authors: CORBO R. M. , INGIANNA R. , SCACCHP R. , BOZZI A. 
Published: September 2007

SummaryRed blood cell S‐adenosylhomocysteine hydrolase (AHCY) from individuals of 1, 2‐1 and 3‐1 phenotypes was partially purified and Km and Vmax determined in the absence and in the presence of the following inhibitors: 3‐deaza‐adenosine (DZA), 3‐deaza‐aristeromycin (DZAry), 2–chloro adenosine (2‐Cl‐ado) and purine riboside (or nebularine). The three phenotypes 1, 2‐1, 3‐1 showed similar Km (32·58, 39·22 and 34·84 μm respectively), but the ratio Km/Vmax was statistically different. DZA and DZAry appeared to be strong competitive inhibitors. The AHCY 1 phenotype was more resistant to their action, while the 3‐1 variant was more sensitive. 2‐Cl‐ado and purine riboside were weaker inhibitors; the type of inhibition varied among the three phenotypes, but, again, the AHCY 1 phenotype was less sensitive than the other two.
Apparent heterozygote deficiencies observed in DNA typing data and their implications in forensic applications
Authors: CHAKRABORTY R. , ANDRADE M. DE , DAIGER S. P. , BUDOWLE B. 
Published: September 2007

SummaryRestriction fragment length polymorphisms (RFLP) analysis using the Southern blot technique can be used to recognize copy number variation of variable number of tandem repeats (VNTR) of conserved core sequences at several regions of the human genome. This new class of polymorphisms reveals a high degree of genetic variation, useful for individual identification purposes. Criticisms against forensic applications of such DNA typing data include the limitation of employing Hardy Weinberg expectation of genotype frequencies, since several surveys indicate apparent deficiency of heterozygosity (or excess homozygosity) in comparison with Hardy‐Weinberg expectations. This research postulates an alternative explanation of deficiency of apparent heterozygosity which is caused by the inability to detect extremely small‐sized alleles (called ‘non‐detectable’ alleles) due to the sensitivity of Southern gel electrophoresis. We show that the presence of ‘non‐detectable’ alleles can produce pseudo‐homozygosity and their frequencies can be predicted from the observed proportional heterozygote deficiency. Furthermore, in the covert presence of such ‘non‐detectable’ alleles, we show that the gene‐count method provides over‐estimates of allele frequencies in the sample population, and hence the Hardy Weinberg predictions of genotype frequencies avoid wrongful bias against suspects in forensic applications of DNA typing data. Applications of this theory to population data on six VNTR loci in US Caucasians and US Blacks suggest that the presence of ‘non‐detectable’ alleles could be the major cause of apparent heterozygote deficiency, and the current approaches of predicting the population frequency of specific DNA phenotypes are practically free of the possible wrongful bias in courtroom applications of DNA typing data.
Mitochondrial and nuclear variants in a U.S. Black population: origins of a hybrid population
Authors: HSIEH C.‐L. , SUTTON H. E. 
Published: September 2007

SummaryThe maternal transmission of mitochondria in higher eukaryotes makes it possible to distinguish between reciprocal matings, since offspring possess the mitochondrial DNA variants received from the mother. This possibility can be extended to hybrid populations, the mitochondrial frequencies reflecting the relative maternal contributions from the parental populations. Nuclear variations reflect the relative genetic contributions of the parental populations, irrespective of parental sex. The U.S. Black population is a hybrid of West African and European populations. The African‐European matings that contributed to the present Black population are traditionally considered to have been almost exclusively between African females and European males. We have studied nuclear and mitochondrial variants in a sample of U.S. Blacks, comparing them with published frequencies from African and Caucasian groups. Our results suggest that the mitochondria of present‐day American Blacks are derived from Caucasians to an extent similar to nuclear genes. In contrast to traditional beliefs, the contribution from Caucasian females is of the same magnitude as that from Caucasian males.
Structure and chromosomal localization of the human 2‘,3’‐cyclic nucleotide 3‘‐phosphodiesterase gene
Authors: DOUGLAS A. J. , FOX M. F. , ABBOTT C. M. , HINKS L. J. , SHARPE G. , POVEY S. , THOMPSON R. J. 
Published: September 2007

SummaryHuman brain cDNA clones for the myelin associated enzyme 2′ 3′ ‐cyclic nucleotide 3′ ‐phosphodiesterase (CNPase) have been isolated and sequenced. The only 5′ untranslated region (UTR) sequence found was that of a human CNPII mRNA, with no direct evidence for a CNPI mRNA. Human CNPase cDNAs were used to isolate genomic clones containing the human CNPase gene which is 9 kb long. Four exons were identified, separated by three introns, and the sequence of each exon and intron/exon boundary has been established.The polymerase chain reaction (PCR) was used to detect the presence of the human CNPase gene in DNA from a panel of rodent/human somatic cell hybrids. By this means the human CNPase gene was mapped to chromosome 17. In situ hybridization of a human CNPase genomic clone to metaphase chromosomes further localized this gene to chromosomal band 17q21.
Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase
Authors: KELLY C. D. , EDWARDS Y. , JOHNSTONE A. P. , HARFST E. , NÓGRÁDI A. , NUSSEY S. S. , POVEY S. , CARTER N. D. 
Published: September 2007

SummaryGlutamic acid decarboxylase (GAD) catalyses the conversion of l‐glutamic acid to the inhibitory neurotransmitter γ‐aminobutyric acid (GABA). Two forms of human GAD, GAD65 and GAD67, are encoded by two separate genes.A full length human GAD67 cDNA has been isolated from a human frontal cortex cDNA library and the nucleotide sequence determined. The GAD67 gene has been mapped to chromosome 2 using the polymerase chain reaction to amplify specifically the human sequence in rodent/human somatic cell hybrid DNA. This confirms that human GAD67 is not syntenic with the smaller GAD isoform GAD65 which has been assigned to chromosome 10. Production of polyclonal antiserum to a baculovirus‐expressed GAD67 enabled immunocytological detection of GAD in the rat brain.
A study on Lu‐null families in South Wales
Authors: ROWE G. P. , GALE S. A. , DANIELS G. L. , GREEN C. A. , TIPPETT P. 
Published: September 2007

SummaryRed cells of 75614 blood donors in South Wales were screened with anti‐Lub revealing 54 Lu(b –) donors of which 15 were also Lu(a –) giving a frequency of 0–0002 for the Lu(a ‐b ‐) phenotype in South Wales. The families of 11 Lu‐null propositi were investigated to determine which of the three known genetic backgrounds, dominant, recessive or X‐linked recessive, was responsible for their Lu–null phenotype. In 10 of the 11 families the Lu–null phenotype was caused by the dominant suppressor gene In(Lu). The first reported family demonstrating independence of In(Lu) and LU, through the Au groups, is described together with the third family demonstrating suppression of P1 by In(Lu). The families showed that In(Lu) is not closely linked to HLA. The genetic background for the 11th propositus was not determined; homozygosity of the silent allele LU is a possible but unproved explanation.
Interphase cytogenetics of the ICF syndrome
Authors: MARASCHIO P. , CORTINOVIS M. , DAINOTTI E. , TUPLER R. , TIEPOLO L. 
Published: September 2007

SummaryInterphase behaviour of centromeric heterochromatin of chromosomes 1 and 16 has been investigated in lymphocytes and fibroblasts of patients with ICF syndrome and of normal subjects with non‐isotopic in situ hybridization, using the satellite II‐related probe pHuR 195.We found evidence for interphase somatic pairing in ICF lymphocytes with a frequency higher than that found in normal cells. Lymphocytes of ICF patients showed nuclear protrusions and micronuclei and these nuclear abnormalities consistently involved a hybridization signal.Somatic pairing was also present in fibroblasts, but with frequencies similar in normal and ICF subjects. The fibroblasts do not have the major chromosomal abnormalities found in lymphocytes.The degree of heterochromatin condensation in fibroblasts was lower than that in lymphocytes and we postulate that the more decondensed state of chromocentres in the fibroblasts could be the reason for the absence of the major chromosomal abnormalities.
Hazard and probabilities of unknown genotypes
Authors: JEANPIERRE M. 
Published: September 2007

SummaryThe likelihood of a genotype of an unsampled individual depends upon genetic data from relatives. When these relatives may be carriers of a mutation as in X‐linked disease, the likelihood of a genotype is altered by the consequences of the possible genotypes on offspring. The probabilities of the possible genotypes are easily derived from the probabilities conditional on the genotype obtained from a computer program aimed at risk calculation. This procedure of genotype reconstruction brings to light a potential hazard in the interpretation of computer data: a compound risk may be better represented as the harmonic mean of a set of conditional probabilities than the simple average of these probabilities.
Genetic polymorphism in the 3‘ ntranslated region of human phosphoglucomutase‐1
Authors: March R. E. , Hollyoake M. , Putt W. , Hopkinson D. A. , Edwards Y. H. , Whitehouse D. B. 
Published: September 2007

SummaryA 317‐bp segment of DNA from the 3′ region of the human phosphoglucomutase‐1 (PGMl) gene has been examined by a non‐radioactive technique for the occurrence of single‐strand conformation polymorphism (SSCP), Eight phenotypes were detected and attributed to the presence of four alleles. Genetic analysis of 75 unrelated individuals and six CEPH families whose PGMl protein phenotypes were known revealed strong association between the PGMl ‘+’ and ‘−’ isozyme phenotypes and the variation detected in this region, but no association with the PGMl 1 and PGMl 2 isozyme phenotypes. DNA sequence analysis demonstrated the presence of three nucleotide substitutions underlying the alleles, which were located in the untranslated region of the PGMl gene. There was complete correlation between the nucleotide sequence and the phenotype detected by SSCP analysis. This study provides support for the model that the PGMl isozyme polymorphism is determined at two distinct sites in the coding sequence, one coding for the ‘1’ and ‘2’ alleles and the other coding for the ‘+’ and ‘−’ alleles, separated by a region where intragenic recombination occurs.
Complex polymorphisms are revealed by Y chromosome probe 49a with BglII, HindIII, PstI and SstI
Authors: SPURDLE A. B. , JENKINS T. 
Published: September 2007

SummaryY chromosome probe 49a detects complex polymorphisms with BglII, HindIII, PstI and SstI, involving 19, 13, 18 and 11 variant bands respectively. The haplotype, a description of the arrangement of fragments in an individual, exhibits great variation. Most haplotypes are population‐specific and occur infrequently. In a study of approximately 60 individuals of Caucasoid, Negroid and San origin, 21, 23, 28 and 24 haplotypes were revealed by BglII, HindIII, PstI and SstI respectively. Reduced genetic diversity in the Negroid population was ascribed to both the proposed recent common origin of the Bantu‐speaking Negroid population from a proto‐Bantu stock and the common practice of polygamy in African Negroids, as were specific correlations between the different polymorphisms within the Negroid population only. In general, no single haplotype for a given enzyme system strictly correlated with a haplotype from any of the other three systems, suggesting that each polymorphism results from a combination of restriction site mutations and rearrangement events. This tremendous variability has potential in paternity testing for male offspring.
The common, Near‐Eastern origin of Ashkenazi and Sephardi Jews supported by Y‐chromosome similarity
Authors: BENERECETTI A. S. SANTACHIARA , SEMINO O. , PASSARINO G. , TORRONI A. , BRDICKA R. , FELLOUS M. , MODIANO G. 
Published: September 2007

SummaryAbout 80 Sephardim, 80 Ashkenazim and 100 Czechoslovaks were examined for the Y‐specific RFLPs revealed by the probes p12f2 and p49a, f on TaqI DNA digests. The aim of the study was to investigate the origin of the Ashkenazi gene pool through the analysis of markers which, having an exclusively holoandric transmission, are useful to estimate paternal gene flow. The comparison of the two groups of Jews with each other and with Czechoslovaks (which have been taken as a representative source of foreign Y‐chromosomes for Ashkenazim) shows a great similarity between Sephardim and Ashkenazim who are very different from Czechoslovaks. On the other hand both groups of Jews appear to be closely related to Lebanese. A preliminary evaluation suggests that the contribution of foreign males to the Ashkenazi gene pool has been very low (1% or less per generation).
Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7
Authors: FOSTER K. , FERRELL R. , KING‐UNDERWOOD L. , POVEY S. , ATTWOOD J. , RENNICK R. , HUMPHRIES S. E. , HENNEY A. M. 
Published: September 2007

SummaryInformative polymorphisms have been very difficult to detect in the elastin gene, and this has hampered the analysis of heritable connective tissue disorders, notably the Marfan syndrome. We have recently detected a dinucleotide repeat polymorphism in intron 17 of the human elastin gene consisting of 8 alleles with sizes between 161 and 175 bp. Analysis of 540 chromosomes from unrelated Caucasian individuals revealed a bimodal frequency distribution typical of (dC‐dA)n (dG‐dT)n repeat polymorphisms, with allele frequencies ranging from 0.004 (161 bp) to 0.574 (163 bp). As the elastin gene was originally assigned to chromosome 2q31‐ter and because more recent data have suggested an assignment to 7q11.1–21.1, we have genotyped a sub‐set of the CEPH pedigrees and carried out pairwise linkage analysis with markers on chromosomes 7 and 2. Lod‐scores of between +3.70 and +13.69 were obtained with markers spanning 7p13‐q22.1, whilst negative lod‐scores were observed with the chromosome 2 markers. Analysis of type II human ovarian teratomas placed the elastin gene within 11 cM of the centromere on chromosome 7. Additionally, we detected the dinucleotide repeat in human‐rodent cell hybrids containing chromosome 7, but not those containing chromosome 2. These data confirm the assignment of elastin to chromosome 7 and provide a new, highly informative marker for the analysis of heritable disorders of connective tissue for which elastin is a candidate gene.
Power comparison of various sibship tests of association
Authors: GREEN J. R. , SHAH S. 
Published: September 2007

SummaryThere are several tests available for use with family studies to test if there is significant evidence of association with a particular disease gene locus, especially of HLA. We have used large simulations to compare the powers of tests using criteria N, R, T, PR, WP and some new tests involving both affecteds and unaffecteds in a sibship. It was found that tests using both affected and unaffected siblings were often more powerful.
A new approach for interpreting the genetic diversity in space: ‘Mobile Site Method’. Application to Gm haplotype distribution of twenty‐seven Amerindian tribes from North and Central America
Authors: HAZOUT S. , GUASP G. , LOIRAT F. , MAURIERES P. , LARROUY G. , DUGOUJON J. M. 
Published: September 2007

SummaryWe present a new approach, called ‘Mobile Site Method’ (MSM), to the construction of ‘genetic similarity maps’ more efficient than that described in a preceding paper (Hazout et al. 1991). After building a triangular mesh between the geographical sites, the method consists of moving these locations at each iteration to reduce the overall differences between the geographic and genetic distances. The genetic similarity map, i.e. the final distorted map, allows the interpretation of the genetic diversity of a population set. We have applied this method to the study of Gm immunoglobulin allotypes of twenty‐seven Amerindian groups from North and Central America. By a local weighted linear regression, we have reconstituted the distorted contour of America. This representation completes the observations of the sites during the map distortion. In this study, we have defined a large geographical factor in the genetic data (84% of the variability explained), related to a linguistic factor.
Lack of RH C/E expression in the Rhesus D– phenotype is the result of a gene deletion
Authors: BLUNT T. , STEERS F. , DANIELS G. , CARRITT B. 
Published: September 2007

SUMMARYWe have investigated the arrangement of genes in the rare Rh (Rhesus) partial null condition D–, Southern blot and PCR studies under conditions which distinguish the highly homologous RH D and RH C/E genes show that in an Icelandic family with the D– haplotype at least 85% of the RH C/E gene is deleted. This finding is in contrast to one other published case of this phenotype, where intact RH D and C/E genes were found, and also to the full amorph Rhnull phenotype, where an intact RH C/E gene was found, accompanied by the deletion of the RH D gene typical of Rh D‐negative individuals.
Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies
Authors: LAWRENCE S. , BEASLEY R. , DOULL I. , BEGISHVILI B. , LAMPE F. , HOLGATE S. T. , MORTON N. E. 
Published: September 2007

SUMMARYTraits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank‐transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two‐locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta‐analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach.
Physical mapping of 38 highly informative genetic markers to 10 intervals of chromosome 11q: integration of the physical and genetic maps
Authors: HUNT D. , HEYNINGEN V. VAN , JONES C. , McCONVILLE C. , BENHAM F. J. 
Published: September 2007

SUMMARYA large number of highly polymorphic microsatellite markers particularly suitable for genetic linkage analysis have recently been developed. In order to facilitate integration of the genetic maps of chromosome 11q generated using these types of markers with the physical maps of 11q currently being assembled, we have regionally assigned the Genethon markers and the 11q designated index plus other commonly used polymorphic markers to ten physical intervals of 11q. These intervals are defined by translocation breakpoints immortalized in somatic cell hybrid lines and can therefore serve as readily accessible and stable landmarks for detailed map integration and facilitate the derivation and placement of new markers and cloned contigs.