bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of genetic variation in two human thyroxine‐binding plasma proteins by immunodetection after isoelectric focusing
Authors: WHITEHOUSE D. B. , HOPKINSON D. A. , HILL A. V. S. , BOWDEN D. K.
Published: September 2007

An immunological method for the detection of two thyroxine‐binding plasma proteins, thyroxine‐binding globulin (TBG) and thyroxine‐binding prealbumin (TBPA), following polyacrylamide gel isoelectric focusing is described. Both proteins show complex electrophoretic patterns, attributable to post‐translational glycosylation, which are affected by unfavourable conditions of sample storage. No genetic variants of TBG or TBPA were encountered in a study of N. European individuals (n= 50). The X‐linked TBG polymorphism, previously detected using a radiolabelled ligand binding technique in Pacific Islanders, was, however, demonstrable by our new immunological method in a previously untested population (n= 139) from the island of Maewo in Vanuatu.
A cytochrome P‐450 gene family mapped to human chromosome 19
Authors: PHILLIPS I. R. , SHEPHARD E. A. , POVEY S. , DAVIS M. B. , KELSEY G. , MONTEIRO M. , WEST L. F. , COWELL J.
Published: September 2007

We have recently isolated a cloned cDNA coding for a cytochrome P‐450 of human liver microsomal membranes, which corresponds to a major phenobarbital‐inducible cytochrome P‐450 of rat liver. This human cytochrome P‐450 is encoded by a member of a multigene family. DNA extracted from a panel of 12 independent human‐rodent somatic cell hybrids was analysed by Southern blot hybridization with the cloned cDNA. The results indicate that all components of this cytochrome P‐450 gene family are located on chromosome 19. Evidence from hybrids derived from an individual carrying a balanced translocation suggests a regional localization of 19p13.2→qter. Analysis of human metaphase chromosomes by in situ hybridization localizes this cytochrome P‐450 gene family further to the long arm of chromosome 19 in the region q13.1→qter. We propose the designation P450PB for this locus.
Absence of significant autosomal lesions in Huntington's disease
Authors: BEVERSTOCK G. C. , MOL A. , WIENHOFER E.
Published: September 2007

Peripheral blood from six patients with Huntington's disease (HD) and six controls were cultured in three types of media known to produce fragile sites. A total of 3000 metaphases per group were scrutinized in a blind coded study. No significantly specific ‘hot‐spot’ was found capable of differentiating between HD patients and controls.
Immunological cross‐reactivity of alcohol dehydrogenase (ADH) isozymes with rabbit immune sera against horse and human ADH subunits
Authors: ADINOLFI A. , MASSA O. , ALESSANDRO G. d'
Published: September 2007

Rabbit immune sera raised against denatured forms of horse liver alcohol dehydrogenase and of human ADH5 isozyme were found to react with the denatured subunits of all the human ADH isozymes regardless of their class.

The immune serum against the human ADH isozyme cross‐reacted also with horse ADH subunits and, at appropriate dilutions, both the immune sera reacted with denatured yeast ADH, suggesting that common structures have been preserved in these molecules over a long evolutionary period.

The immune sera partially reacted also with the respective antigens in their native conformation, indicating that some ‘sequential ’ epitopes are expressed on the surface of the folded proteins.
Genetic polymorphism of esterase B3 in human leukocytes
Authors: COATES P. M. , CORTNER J. A.
Published: September 2007

Human tissues contain an esterase activity called ESB3, detectable by starch gel electrophoresis followed by staining with α‐naphthyl butyrate. Using mononuclear leukocytes, we demonstrated an electrophoretic variant of ESB3. Family studies suggest that the variant is inherited as a simple Mendelian trait; individuals with the ESB3 2‐1 phenotype are heterozygotes, designated ESB31ESB32, to distinguish them from the more common homozygotes, ESB31ESB31. The frequency of the ESB32 allele is estimated to be 0.035 in U.S. Whites. No homozygotes for this allele have yet been found.

Our studies suggest that the enzyme from ESB3 1 individuals exists primarily as a trimer of three identical subunits with a molecular weight of approximately 58000 daltons. The genetic variant (ESB32 allele) appears to be the result of a mutation that does not affect the charge of the subunit, but rather reduces its ability to form and maintain the trimeric structure.
Assignment of the human gene for β‐glycerol phosphatase to chromosome 8
Authors: WILSON D. E. , PIZZO R. DEL , CARRITT B. , POVEY S.
Published: September 2007

The segregation of the human gene for β‐glycerol phosphatase (GPB) was examined in human‐Syrian hamster and human‐Chinese hamster somatic cell hybrids. Electrophoretic analysis of the GPB in hybrids suggested that the enzyme is a dimer. Human GPB cosegregated with chromosome 8 in the twenty‐five hybrids examined.
Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1
Authors: SWALLOW D. M. , POVEY S. , PARKAR M. , ANDREWS P. W. , HARRIS H. , PYM B. , GOODFELLOW P.
Published: September 2007

The gene coding for the liver/bone/kidney isozyme of alkaline phosphatase, ALPL, has been mapped to human chromosome 1 using a monoclonal antibody TRA‐2–54/2J and electrophoretic analysis to distinguish between the human and rodent isozymes in human/rodent somatic cell hybrids.
Regional localization of a human cytochrome P‐450 (CYP1) to chromosome 19q 13.1–13.3
Authors: DAVIS M. B. , WEST L. F. , SHEP HARD E. A. , PHILLIPS I. R.
Published: September 2007

A phenobarbitone inducible cytochrome P‐450 gene family (CYP1) has recently been localized to chromosome 19q13.1‐qter. We have used a human liver cDNA probe in in situ hybridization experiments to metaphase chromosomes from two balanced translocation carriers, 46, XX, t(11;19) (q13;q13.1) and 46, XX, t(7;19) (q31.3;q13.3) to obtain a more precise localization. The results suggest a regional assignment for CYP1 to chromosome 19q13.1–13.3.
A speculative model for the Rh blood groups
Authors: TIPPETT P.
Published: September 2007

Two closely linked structural loci, D and ‘CcEe’, are proposed as the basis of the Rh blood groups. Mutation and unequal crossing‐over between the two loci at meiosis are considered as possible explanations for some rare Rh complexes. The theory predicts that complexes arising from unequal crossing‐over would be expected to have aberrant Rh polypeptides.
A method of subdividing genetic data into self‐contained subsets
Authors: LI C. C.
Published: September 2007

A method of subdividing genetic data into self‐contained subsets has been described in terms of examples. The subsets are such that each of them permits a valid estimate of the parameter concerned. Hence, the discarding of one or more subsets would not affect the validity of the remaining data. The detailed statistical properties of such subsets await further investigation. There is a need to simplify the variance formulas for estimates based on partial data.
Mitochondrial DNA polymorphisms in Italy I. Population data from Sardinia and Rome
Authors: BREGA A. , SCOZZARI R. , MACCIONI L. , IODICE C. , WALLACE D. C. , BIANCO I. , CAO A. , BENERECETTI A. S. SANTACHIARA
Published: September 2007

The polymorphisms of human mitochondrial DNA were studied in about 150 Sardinians from Cagliari and 100 other Italians living in Rome, using total blood cell DNA and the following restriction enzymes: HpaI, BamHI, HaeII, MspI, AvaII and Hinc II.

1. Seven different new morphs have been identified, one for Hae II, four for AvaII and two for Hinc II.

2. 16 and 17 mtDNA types were observed in the Sardinian and Roman samples, respectively. Of these only seven were shared by both groups. The morphs BamHI‐3, MspI‐4 and AvaII‐9 were found associated at a frequency (100%) much higher than expected (0.17%).

3. Sardinians can be differentiated from the other Italians for a higher frequency of both morph AvaII‐1(P < 0.05) and type 1 (2–1–1–1–1) (P0.03), and for a lower intragroup heterogeneity (0.52 v. 0.61).

4. The Italian sample on the whole can also be differentiated from the Caucasian group previously examined for a lower frequency of BamHI morph 2 (PYates < 0.01), a higher frequency of HaeII morph 1 (PYates < 002) and for the presence at a non‐negligible incidence (5 inviduals out of 229) of the new type 57–2 (2–3–1–4–13–2).

The data indicate that mtDNA polymorphisms have not only proved to be a useful tool in detecting differences among major human groups but they can also differentiate populations within the same major ethnic division.
The affected sib method. V. Testing the assumptions
Authors: LOUIS By E. J. , PAYAMI H. , THOMSON G.
Published: September 2007

The affected sib methods, which are used to make inferences about the genetic components of HLA associated diseases, have many underlying assumptions which may not always be realistic. These include no selective disadvantage of affected individuals, little or no recombination between the marker loci and the ‘disease’ locus, a single panmictic population, Mendelian segregation of the disease locus alleles and random distribution of individuals over environments. The effects of breaking these assumptions have been investigated. We have explicitly derived the haplotype sharing identity by descent (IBD) expectations for the cases of selection against affected individuals and recombination between the HLA marker loci and the ‘disease’ predisposing locus for affected sib trios (as was previously done for affected sib pairs). We have also derived, for both affected sib pairs and trios, the haplotype sharing expectations for non‐random mating (positive assortative), admixture, meiotic drive (of disease allele carrying haplotypes), and a random versus shared environmental component for sibs. In order to assess the sensitivity of the affected sib methods to perturbations in the assumptions, the expectation spaces of haplotype sharing in affected sib pairs and sib trios under the single diallelic locus model with varying penetrances and allele frequencies are fully described. The effects on haplotype sharing and subsequent disease parameter estimation are different for each of the factors we have considered. The affected sib methods are found to be robust in many situations.
The use of measured genotype information in the analysis of quantitative phenotypes in man.
Authors: BOERWINKLE E. , SING C. F.
Published: September 2007

We have begun a measured genotype approach to the genetic analysis of lipid and lipoprotein variability. This approach enables one to simultaneously estimate the frequencies and effects of alleles at specific loci along with the residual polygenetic variance component. In this study we consider the contribution of three common alleles at the locus coding for apolipoprotein E to interindividual variation of total cholesterol, betalipoprotein, and triglyceride levels. A sample of 102 nuclear families consisting of 434 individuals was studied. The frequencies of the ε2, ε3, and ε4 alleles in this sample are 0·137,0·740, and 0·123, respectively. In separate analyses of cholesterol and betalipoprotein levels, a complete model that includes the effects of the six apo E genotypes, unmeasured polygenes, and individual specific environmental effects fits these data significantly better than a reduced model that does not include the effects of the apo E polymorphism or a reduced model that does not include the effects of polygenes. On the average the ε2 allele lowers total cholesterol and betalipoprotein levels by 0·425 mmol/l and 0·811 units, respectively. The ε4 allele is associated with an average increase of these phenotypes by 0·255 mmol/l and 0·628 units, respectively. Simultaneous estimates of the interindividual variability of total cholesterol levels attributable to the apo E polymorphism and to residual polygenic effects are 8% and 56%, respectively. For betalipoprotein levels, we simultaneously estimate these values to be 7% and 42%, respectively. A reduced model including the effects of polygenes but not the effects of the apo E polymorphism fitted the triglyceride data as well as the complete model. The estimate of the fraction of interindividual variability associated with polygenetic effects was 26.5%. We review our present understanding of the genetic architecture underlying variability of cholesterol levels in the population at large and infer that the majority of the genetic variability may be accounted for by polymorphic gene loci with moderate effects on cholesterol levels.
The locus ordering problem
Authors: EDWARDS J. H.
Published: September 2007

Studies of phenotypes defined by codominant alleles at two or more loci in three‐generation families allow haplotypes to be deduced. These data are easily summarized by the Mendelian convention of upper and lower case, with case defining phase rather than nature. In two‐generation families haplotypes may be inferred with high precision for closely linked loci even if an allele at one locus is recessive.

Coding procedures are discussed and a simple solution to inferring the most likely order of three or more loci, and defining its likelihood compared with other orders, is presented.
The effect of non‐random migration on genetic differences between populations
Authors: ROGERS A. R. , JORDE L. B.
Published: September 2007

Models of genetic population structure generally assume that emigrants from each local group are drawn at random from the set of individuals born there. We show that small violations of this assumption can have disproportionately large effects on genetic population structure, and we introduce a statistical method for measuring this effect.
Genetic studies of low abundance human plasma proteins VIII. Inherited structural variation in antithrombin III
Authors: KAMBOH M. I. , FERRELL R. E.
Published: September 2007

Genetically determined structural polymorphism of antithrombin III has been observed using ultra narrow pH polyacrylamide isoelectric focusing gels, followed by immunoblotting. The products of three alleles at the antithrombin III structural locus have been detected in normal U.S. white and black blood donors. The frequencies of the three alleles, AT III*1, AT III*2 and AT III*3, respectively, are: 0.878, 0.103, 0.019 in whites and 0.916, 0.068, 0.016 in blacks. Family data from a large number of families establish an autosomal codominant pattern of inheritance of the three alleles.
Mitochondrial DNA polymorphisms in Italy II. Molecular analysis of new and rare morphs from Sardinia and Rome
Authors: BENERECETTI A. S. SANTACHIARA , SCOZZARI R. , SEMINO O. , TORRONI A. , BREGA A. , WALLACE D. C.
Published: September 2007

A molecular analysis of morphs found in a previous survey of mtDNA restriction enzyme polymorphisms in Italy revealed that different site changes can give similar patterns and that the same mutation can yield variant morphs for apparently unrelated enzymes.

1. Alternative site variations were found to yield restriction fragment patterns resembling HpaI morph 4, HaeII morph 5 and AvaII morph 2.

2. A strong association was observed between the BamHI morph 3 (gain of site a) and the AvaII morph 9 and its derivatives (loss of site d). This association appears to result from an A to G transition at base pair (bp) 13368 which simultaneously creates a new BamHI site and abolishes an AvaII site. On the other hand, the loss of the AvaII site d, which in Italy was only found in the above‐mentioned association, does not always produce a new BamHI site, as observed in other Caucasian groups. Similarly, the Bam HI morph 2 (gain of site b) was always found to be associated with AvaII morphs lacking site f. An A to G transition at bp 16391 was shown to account for both changes. As in the previous case, the converse is not true. Hence, these data show that AvaII sites d and f were lost in more than one way and one of these seems to be typical of Caucasians.

3. The variation producing BamHI‐3/AvaII‐9 and derivatives is preferentially associated with MspI morph 4 but this is not a product of a shared mutation. Hence, this association must be the result of the linkage disequilibrium due to the maternal inheritance of mtDNA and lack of recombination.

4. The high frequency of the combination BamHI‐3/AvaII‐9 and derivatives with MspI‐4 found in Italy (29 subjects out of 229 analysed) can best be explained by diffusion of the relevant haplotype rather than by repeated mutational events.

5. The phylogeny trees of all mtDNA morphs so far described and of mtDNA types in Caucasians have been revised taking into account both the inter‐ and the intra‐morph heterogeneity detected by this analysis.
Regional assignment of the gene coding for human sucrase‐isomaltase (SI) to chromosome 3q25‐26
Authors: WEST L. F. , DAVIS M. B. , GREEN F. R. , LINDENBAUM R. H. , SWALLOW D. M.
Published: September 2007

The gene coding for sucrase‐isomaltase (SI) has recently been mapped to chromosome 3 using a cDNA probe to analyse DNA from somatic cell hybrids (Green et al. 1987). We have now used this same cDNA probe to obtain a regional localization of this gene. In situ hybridization to normal metaphase chromosomes and to chromosomes from individuals with balanced translocations suggests a regional assignment to chromosome 3q25‐26.
Two methods for measuring the non‐randomness of chromosome abnormalities
Authors: BRAEKELEER M. DE , SMITH B.
Published: September 2007

Applying conventional statistical techniques to cytogenetic data usually faces the problem of working with small numbers and many classes. We describe two techniques, one based on a binomial test procedure, the other on Monte Carlo simulations, aimed at studying the non‐randomness of chromosomal aberrations. Both techniques were used to study the distribution of breakpoints involved in variant Philadelphia translocations in chronic myeloid leukaemia. The results showed that 28 bands were non‐randomly rearranged (P 0.05). Furthermore, the probabilities calculated from the binomial test procedure were close to those calculated from the Monte Carlo simulations.
Origin of sex chromosome aneuploidy
Authors: MORTON N. E. , WU D. , JACOBS P. A.
Published: September 2007

Probabilities applicable to RFLPs are derived for the genotypes of XXY, XXX, and XO children, conditional on their mode of origin and the parental mating type, and the theory is applied to family data on the XG locus. The proportion of XXY males arising in spermatogenesis is shown to be 0.41 ± 0.09. The large distance of XG from the centromere makes distinction between maternal meiosis I and II unreliable, but if man is like Drosophila, most of the maternal non‐disjunctions arise in meiosis I, among tetrads that have undergone one or more exchanges. Data from XG show that 0.78 ± 0.05 of XO females arise from an error involving the paternal sex chromosomes. The XG locus is virtually uninformative about the origin of XXX. Application of the theory to selected RFLPs will be much more incisive because of their large number, lack of dominance, greater heterozygosity, and distribution along the chromosome. Study of RFLPs will facilitate diagnosis of the parental origin of sex chromosome abnormalities and the comparison of recombination rates in regular and trisomic progeny of maternal mei I and mei II origin.

A pseudocentromeric model that estimates map distances from exceptional progeny is applied to non‐disjunction of the X chromosomes in D. melanogaster, giving good recovery of the expected map and thereby validating this approach for RFLPs in man.
N‐ras‐like sequences on chromosomes 9, 6 and 22 with a polymorphism at the chromosome 9 locus
Authors: MIDDLETON‐PRICE H. , SPURR N. , HALL A. , MALCOLM S.
Published: September 2007

Two clones, pCN1 and pCN2, which together form full‐length cDNA for N‐ras, were used to search for restriction fragment length polymorphisms. pCN2, which entirely consists of 3′ non‐translated sequences, revealed more bands on DNA transfer hybridizations than could be accounted for using the known restriction map of N‐ras. None of the extra cross hybridizing sequences is located on chromosome 1. One of these sequences showed a high‐frequency two‐allele polymorphism with the restriction enzyme TaqI and maps to the short arm of chromosome 9. Of the remaining two sequences, one maps to chromosome 22 and the other maps to the short arm of chromosome 6. pCN1A, which contains the 5′ untranslated regions and all the coding exons of N‐ras only hybridized to the chromosome 1 site. No polymorphisms have been found for pCN1 with TaqI, MspI, BclI, BglI, EcoRI, BstXI, XbaI, BamHI, BglII or HindIII.
Diversity of some gene frequencies in European and Asian populations. IV. Genetic population structure assessed by the variogram
Authors: BARBUJANI G.
Published: September 2007

Isolation‐by‐distance models of population structure predict an exponential decrease of genetic relatedness with distance. Under the Kimura‐Weiss (1964) model the plots of gene frequency variance versus distance (variograms), computed at various loci, are expected to have equal slope and reach a common asymptote. The gene frequency distributions at eight loci in 192 European and Asian populations have been summarized by variograms. On the average, the Kimura‐Weiss model seems to describe adequately allele frequency change up to 900 km, but gradients are apparent at greater distances for most markers studied. These patterns may result form either differential selection or long‐range gene flow; however, the extensive clinal variation observed for glyoxalase, esterase D and 6‐PGD cannot be entirely accounted for by the Neolithic radiation of early farmers in the Middle East and Europe.
Maternal age in trisomy
Authors: MORTON N. E. , JACOBS P. A. , HASSOLD T. , WU D.
Published: September 2007

By comparison with a more general theory, data on trisomy in live births, amniocenteses, and spontaneous abortions by year of maternal age are shown to fit a logistic augmented by a proportion independent of maternal age. The frequency of trisomy increases monotonically, with no discrepancy at extremely low or high maternal age. Trisomy 16 is exceptional in that all cases appear to be age‐dependent. For groups A, B, and C most trisomies arise by a process independent of maternal age. A small proportion of these trisomies and about half of trisomies for smaller chromosomes (excluding trisomies 16 and perhaps 22) originate by some process dependent on maternal (but not paternal) age and therefore presumably independent of crossingover, which in the female takes place before birth.
Detection of linkage between a quantitative trait and a marker locus by the lod score method: sample size and sampling considerations
Authors: DEMENAIS F. , LATHROP G. M. , LALOUEL J. M.
Published: September 2007

A simulation study is here conducted to measure the power of the lod score method to detect linkage between a quantitative trait and a marker locus in various situations. The number of families necessary to detect such linkage with 80% power is assessed for different sets of parameters at the trait locus and different values of the recombination fraction. The effects of varying the mode of sampling families and the sibship size are also evaluated.
Linkage between the expressed hypervariable gene locus PUM and the gene coding for the Duffy blood group FY
Authors: SWALLOW D. M. , GRIFFITHS B. , NOADES J. , CORNEY G.
Published: September 2007

Linkage is reported between the expressed hypervariable gene locus PUM and the gene coding for the Duffy blood group FY, with a maximum lod score of 4 at θ= 0. Linkage can be excluded between PUM and PEPC at a distance of 10 cm.
Close linkage of PUM and SPTA within chromosome band 1q21
Authors: MIDDLETON‐PRICE H. , GENDLER S. , MALCOLM S.
Published: September 2007

Nine families were examined for linkage on chromosome 1 between the hypervariable gene PUM and the α‐spectrin (SPTA) gene using DNA probes. Close linkage was found with a maximum lod score of 5.98 at θ= 0.05.

Hybridization to DNA from somatic cell hybrids made from a parent line carrying a balanced X:1 translocation showed both genes to lie proximal to the breakpoint at 1q23. DNA hybridization to cell lines carrying deletions of 1q21–25 showed the presence of two polymorphic alleles for both loci. These results, combined with existing in situ hybridization data, suggest PUM and SPTA both lie within 1q21.

Linkage analysis between PUM and the Duffy blood group (FY) gave a maximum lod of 2.15 at θ= 0.15. These data combined with data from another laboratory give a maximum lod of 5.21 for linkage between PUM and FY at θ= 0.10
Multipoint mapping and the emperor's clothes
Authors: MORTON N. E.
Published: September 2007

On the hypothesis of no interference, pedigree probabilities for segregating loci considered simultaneously factor into pairwise probabilities, and multipoint mapping reduces to multiple pairwise mapping. Under these conditions, use of a computer program such as linkage or mapmaker entails no gain but substantial loss (measured as map distortion, wasted data, concealed evidence, redundant calculation and exaggerated multiple recombination) by comparison with maps based on lod scores. This is illustrated by the current maps of chromosomes 1 and 2.
Isozyme and DNA analysis of human S‐adenosyl‐L‐homocysteine hydrolase (AHCY).
Authors: ARREDONDO‐VEGA F. X. , CHARLTON J. A. , EDWARDS Y. H. , HOPKINSON D. A. , WHITEHOUSE D. B.
Published: September 2007

Erythrocyte and tissue isozymes of human AHCY have been studied by starch gel electrophoresis, cellulose acetate electrophoresis, isoelectric focusing and Na dodecyl sulphate electrophoresis. The same isozyme was observed in all the tissues studied, suggesting that human AHCY is encoded by a single structural locus. Two variant alleles were identified in erythrocyte AHCY using starch gel electrophoresis in a sample of 166 unrelated individuals from the British population. The gene frequencies were 0–024 for AHCY*2 and 0.006 for AHCY *3. The variant isozyme patterns could not be distinguished by isoelectric focusing.

Using the homologous rat cDNA AHCY probe, human AHCY cDNA recombinants were isolated from a placental cDNA library. The human and rat sequences show considerable homology in the coding region of the gene and also, but to a lesser extent, in the distal part of the 3′ untranslated region. Preliminary observations suggest the occurrence of a high frequency PvuII site RFLP identified with the human AHCY probe.
Genetic analysis of C4 polymorphism by use of DNA amplification (PCR), allele‐specific oligonucleotide probes and allele‐specific restriction enzymes
Authors: BERG E. S. , TEISBERG P. , OLAISEN B.
Published: September 2007

In witro DNA amplification allows multiplication of selected gene segments thereby improving the sensitivity in DNA analysis. Different allelic variants in the amplified DNA may be disclosed either by subsequent hybridization with allele‐specific oligonucleotides or by subsequent allele‐specific digestion with selected restriction endonucleases, followed by separation in agarose gel electrophoresis.

The genes that code for human complement component C4 are polymorphic. Presently we demonstrate that allelic differences in C4, involving one base pair only, can be efficiently identified in the amplified DNA by each of the two techniques. A combination of both techniques may also be employed. The DNA amplification procedure may give access to selected ‘haploid’ fragments for individual DNA studies.
Evidence for a human mitotic mutant with pleiotropic effect
Authors: PAPI L. , MONTALI E. , MARCONI G. , GUAZZELLI R. , BIGOZZI U. , MARASCHIO P. , ZUFFARDI O.
Published: September 2007

Male and female sibs born to third‐cousin parents presented with mental retardation, microcephaly, short stature, juvenile onset limb‐girdle muscular dystrophy and multiple chromosome mosaicism in lymphocytes and fibroblasts. Different aneuploidies (mostly trisomies) were found in 15–20% of the cells and trisomies for the chromosome 8 and chromosome 7 predominated in lymphocytes and fibroblasts respectively, while monosomies were rare. Increased cellular death due to aneuploidy could explain symptoms such as mental and growth retardation and microcephaly. This could be an instance of an autosomal recessive mitotic mutant, possibly affecting a protein simultaneously involved in spindle apparatus and muscle function.
The locus positioning problem
Authors: EDWARDS J. H.
Published: September 2007

The likelihood method of optimizing the position of loci within a given order using data from pairs of loci is discussed in relation to Fisher's paper of 1922 and to recent data on chromosome 22 in man.
A new genetic polymorphism in the 16S ribosomal RNA gene of human motochondrial DNA
Authors: MEHTA A. B. , VULLIAMY T. , GORDON‐SMITH E. C. , LUZZATTO L.
Published: September 2007

Sequence analysis of the 3′ end of the 16s rRNA gene of mitochondrial DNA (mtDNA) revealed a single base change G ‐ A, at position 3010. This mutation was first identified in a patient who had recovered from chloramphenicol‐ induced aplastic anaemia (CAP‐ induced AA). A link between this mutation and CAP‐induced AA was ruled out by investigating three other similar patients, none of whom had the mutation. This mutation lies within or near the chloramphenicol binding site in a part of the 16S rRNA gene which shows high evolutinary conservation and where polymorphisms have not been previosuly reported. Hybridization tests with appropriate oligonucleotide probes in 114 individuals reveal that this mutation has polymorphic frequency of about 14% in Europeans.
Restriction fragment length polymorphism of human mitochondrial DNA in a sample population from Apulia (Southern Italy)
Authors: BENEDICTIS G. DE , ROSE G. , PASSRINO G. , QUAGLIARIELLO C.
Published: September 2007

Restriction fragment length polymorphism (RFLP) of human mitochondrial DNA was analysed in a sample of 87 subjects from Apulia (South Italy) by the restriction enzymes HpaI, BamHI, HaeII, MspI, AvaII, and HincII using total blood cell DNA probed by human mtDNA from placenta. Five BamHI morphs were observed, two of which are new (BamHI‐4 and ‐5), as well as one new AvaII morph (AvaII‐28). The association BamHI‐4/AvaII‐28 enables us to demonstrate for the first time two polymorphic BamHI sites present together in the same mtDNA molecule. In agreement with historical data the Apulian sample has been shown to be the most heterogeneous Italian population so far tested.
Mitochondrial DNA polymorphism detected with the restriction enzymes BstNI and BclI in a French Canadian population
Authors: GÉLINAS Y. , TURCOTTE L. , BOUCHANRD C. , THIBAULT M‐C. , DIONNE F. T.
Published: September 2007

The enzymes BstNI and Bell were used to detect various human mitochondrial DNA RFLPs in a sample of 104 unrelated French Canadians. These sequence variations were found in total white blood cell DNA probed with whole human mitochondrial DNA. With BstNI, 6 mitochondrial DNA restriction patterns (morphs) were identified. BstNI morphs 2–6 each differ from morph 1 by one single distinct restriction site gain or loss on the mitochondrial DNA molecule. Although BstNI morph 1 was found in most of the subjects (80%), each other morph was observed at a frequency of at least 3%. With the enzyme BclI, 4 different morphs were detected. Morphs 2–4 also result from different single restriction site alteration as compared with BclI morph 1. The morph 1 was clearly the most frequent (95%) while morphs 3 and 4 were present in only 1% of the subjects. These data indicate that the enzyme BstNI and, to a much lesser extent, the enzyme BclI detect mitochondrial Dn'A polymorphism in Caucasians. They are therefore of interest for population genetics studies.
Recursive descent probabilities for rare recessive lethals
Authors: THOMPSON E.A. , MORGAN K.
Published: September 2007

Recursively computed descent probabilities provide an effective way to evaluate possible ancestries of rare alleles segregating in large and complex genealogies, but they ignore information other than the descent to a small set of current gene copies. We show how descent probability computations can be modified to incorporate the fact that no ancestor can be affected by a lethal recessive trait. This methodology is applied to two rare recessive traits segregating in a complex Hutterite (Lehrerleut) genealogy.
Analysing rearrangement breakpoint distributions by means of binomial confidence intervals
Authors: VASARHELYI K. , FRIEDMAN J.M.
Published: September 2007

Non‐randomness in the distribution of rearrangement breakpoints can be assessed by means of a binomial probability model. Using the binomial model, we compute confidence intervals for the observed number of breakpoints in chromosome bands and use these confidence intervals to test for non‐randomness in set of 452 constitutional rearrangement breakpoints. This method is useful because it describes the observed data and is not dependent on comparison with a pre‐existing hypothesis regarding the distribution.
Chromosomal mapping of a human phenol UDP‐glucuronosyltransferase, GNT1
Authors: HARDING D. , JEREMIAH S. J. , POVEY S. , BURCHELL B.
Published: September 2007

A 5' fragment of a full‐length cDNA clone encoding a human phenol UDP‐glucuronosyltransferase was used to produce a specific probe for this gene. DNA isolated from a panel of 18 human‐rodent somatic cell hybrids was analysed by Southern‐blot hybridization. The results indicate that this UDP‐glucuronosyltransferase is encoded by a single gene, designated GNT1, located on human chromosome 2.
The gene for the α2 chain of the human fibrillar collagen type XI (COL11A2) assigned to the short arm of chromosome 6
Authors: LAW M. L. , CHAN S. D. H. , BERGER R. , JONES C. , KAO F. T. , SOLOMON E. , CHEAH K. S. E.
Published: September 2007

A cosmid clone (CosHcol.11) containing the α2(XI) collagen gene (COL11A2) has been isolated. The gene contains conserved DNA and amino‐acid sequences characteristic of fibril forming collagen, which is in accordance with the classification of type XI collagen as a fibrillar collagen. The genomic clone containing the α2(XI) gene has been used as probe in the Southern blot analysis of DNA from a panel of human/hamster somatic cell hybrids containing different numbers and combinations of human chromosomes. Synteny analysis revealed that only chromosome 6 showed complete concordant segregation with C0L11A2. Furthermore, the gene was regionally mapped to the short arm of chromosome 6 by using a hybrid which contained only the long arm of the chromosome.
Surname versus gene structure of a small isolate
Authors: PRESCIUTTINI S. , PAOLI G. , FRANCESCHI M.
Published: September 2007

A hierarchical partition of the Wright coefficient of inbreeding (F) is shown for an isolated population (about 2000 inhabitants) from a mountainous region of Tuscany (Italy) with regard to both surnames and genes. At total population level surname variation proves substantially consistent with the observed genetic differentiation of the isolate. Analysis of parental isonymy reveals that the population is structured in subunits and it is concluded that the unit population of the region may be very small, practically coinciding with the village (less than 500 inhabitants). The agreement of ‘demographic’ and genetic structures is less satisfactory at this level, partly because of subsample size, but we conclude that analysis of surnames may give at least a rough idea of the genetic structure of the population.
Wilson's disease in Israel: a genetic and epidemiological study
Authors: BONNÉ‐TAMIR B. , FRYDMAN M. , AGGER M. S. , BEKEER R. , BOWCOCK A. M. , HEBERT J. M. , CAVALLI‐SFORZA L. L. , FARRER L. A.
Published: September 2007

Clinical and family history data on persons affected with Wilson disease (WD) living in Israel between 1958 and 1984 were ascertained from the literature, hospital records and neurological and gastroenterological clinics. From this population of 51 families, representing a diversity of Middle Eastern, North African and European backgrounds, blood samples were collected from affected individuals in 21 families, their parents, sibs and other relatives for quantitative determinations of plasma copper and ceruloplasmin, liver tests and DNA analysis. Although the majority of patients have the hepatic form of the disease, hepatic and neurological cases were found among all ethnic groups. In fact, affected sibs in several inbred families who most likely inherited two copies of the same mutant allele had different symptoms. Gene frequencies were calculated for each of the populations taking into account inbreeding, probability of ascertainment, and estimated incidence. Although many of these communities have gene frequencies which are comparable to worldwide estimates, high prevalence of disease is maintained by consanguineous mating patterns. Probabilities of WND genotypes were calculated for 129 unaffected relatives who had an a priori risk of inheriting at least one WND allele using information from 10 DNA markers closely linked to the WND locus. There was no evidence that multiple loci are responsible for the observed clinical variability in this sample of families. Furthermore, studies of serum copper and ceruloplasmin levels in unaffected relatives suggest that phenotypic variability in WD may be due in part to an interaction of the WND locus with other genetic or non‐genetic modifiers such as age.
The human Y chromosome shows a low level of DNA polymorphism
Authors: MALASPINA P. , PERSICHETTI F. , NOVELLETTO A. , IODICE C. , TERRENATO L. , WOLFE J. , FERRARO M. , PRANTERA G.
Published: September 2007

Six new Y‐specific probes have been isolated and are reported. Along with another six already described they have been used in a systematic search for male specific RFLPs. An overall number of 46515 nucleotides have been screened with 12 enzymes and no polymorphic pattern observed. Our data reveal a greatly reduced level of polymorphism compared with other chromosomes.
On avoiding statistical bias in linkage‐based counselling
Authors: RENWICK J. H.
Published: September 2007

Using the Succession Rule of Laplace (1795) and related reasoning, this paper shows how to give unbiased counselling to patients when predictions are to be based on small samples. The recombination fraction can be regarded as a probability parameter, θ, which itself has a probability distribution between the limits of 0 and 1/2. The probability of a recombinant, P(Rec), is not numerically equal to the maximum likelihood estimate of θ, nor is it numerically equal to the maximum posterior probability estimate in Bayesian inference. Rather it is equal to the infinite sum of all possible θ values, each weighted according to its probability density p(θ) which denotes the relative probability that that θ value is the true one.

The various published proposals for obtaining an unbiased estimate of θ are shown to be equivalent one to another, except for the simplifying approximations used.
Mitochondrial DNA polymorphisms among Hindus: A comparison with the Tharus of Nepal
Authors: SEMINO O. , TORRONI A. , SCOZZARI R. , BREGA A. , BENERECETTI A. S. SANTACHIARA
Published: September 2007

The polymorphisms of mitochondrial DNA for the restriction enzymes Hpal, Bamill, Haell, Mspl, Avail and Hindi were studied in a sample of 79 Hindus, 45 from New Delhi (India) and 34 from Terai (Nepal), both to characterize another Caucasian population and to investigate some possible Hindu component in the genetic structure of the Tharus, a Nepalese population, the anthropological position of which is still disputed.

1. A new BamHI polymorphism was detected; about 5 % of the Hindu mtDNAs have lost the site at 14258 bp and lack any BamHI site. Once again a BamHI polymorphism was found in a Caucasian population.

2. New site mutations were found to yield morphs previously described (MspI‐7,AvaII‐18).

3. Variant morphs for two different enzymes were found due to a shared mutation (morphs BamHI‐O/AvaII‐30 and morphs MspI‐7Hindu/AvaII‐18Hindu).

4. Comparison between Hindu and Tharu data does not show any evidence of a specific Indian component in the Tharu genetic structure and allows us to conclude that Tharus are clearly differentiated from modern Hindus.
Genetic linkage between the Kell blood group system and prolactin‐inducible protein loci: provisional assignment of KEL to chromosome 7
Authors: ZELINSKI T. , COGHLAN G. , MYAL Y. , SHIU R. P. C. , PHILIPPS S. , WHITE L. , LEWIS M.
Published: September 2007

The Kell blood group locus (KEL) is tightly linked to the prolactin‐inducible protein locus (PIP) with ẑ=9.12 at ô= 0.00 for combined paternal and maternal meioses. In view of the regional localization of PIP to 7q32‐q36 (Myal et al. 1989a), a similar assignment for KEL is favoured.
Genetic similarity maps and immunoglobulin allotypes of eleven populations from the Pyrenees (France)
Authors: HAZOUT S. , DUGOUJON J. M. , LOIRAT F. , CONSTANS J.
Published: September 2007

The genetic heterogeneity of eleven populations from the Pyrenees (France) based on the polymorphism of the immunoglobulin allotypes is studied by means of a ‘genetic similarity map’. The method described here, called ‘Mobile Node Metho’, allows the deformation of a square grid, in which the studied region is represented, by moving the nodes at each step in order to reduce the difference between the geographic and genetic distances. This tool allows the overall quantification of the genetic heterogeneity of a population set and possibly the study of its dynamics. Other maps constructed to complete the interpretation are ‘map of moving vectors’, ‘iso‐displacement curves’ and ‘site displacements’. This study identified an overall genetic homogeneity among the Pyrenean populations and several local genetic heterogeneities in different regions.
Family data determine all parameters in Mendelian incomplete penetrance models
Authors: WHITTEMORE A. S. , KELLER J. B. , WARD M. J.
Published: September 2007

We show that data on the frequency of occurrence of an hereditary trait in family members can be used to determine all four parameters in a Mendelian genetic model with incomplete penetrance. Thus previous statements in the literature that such data can determine only three combinations of the parameters are incorrect.
Detection of the common alpha‐1‐antitrypsin variants by denaturing gradient gel electrophoresis
Authors: JOHNSON P. H. , CADIOU H. , HOPKINSON D. A.
Published: September 2007

The well‐characterized and highly polymorphic human alpha‐1‐antitrypsin (AAT) gene was used as a test locus to evaluate the general applicability of denaturing gradient gel electrophoresis (DGGE) for the detection of single base change polymorphisms. We report the resolution of all the major alleles, M1 Ala, M1Val, M2, M3, S and Z and the identification of substantial genetic polymorphism in intron 3–4 by this technique. DGGE was found to be a quick and efficient method for the screening of multiple samples for the presence of genetic variation.
Confirmation of the assignment of the vitronectin (VNRA) and fibronectin (FNRA) receptor α‐subunits
Authors: SPURR N. K. , ROOKE L.
Published: September 2007

The receptors for the extracellular structural components fibronectin and vitronectin each consist of two subunits called α and β. Using human‐rodent somatic cell hybrids and cDNA probes corresponding to the α‐subunits, we have confirmed the mapping of the fibronectin receptor (FNRA) to chromosome 12 and the vitronectin receptor (VNRA) to chromosome 2.
Gene maps and location databases
Authors: MORTON N. E.
Published: September 2007

A location database is defined in linear space by a vector of genetic and physical locations for each locus, which may be ordered by virtual sorting on composite location. This contrasts with an interval database defined in metric space, for which location must be inferred by list‐processing from numbered intervals which are assigned different ordinals in different tables and overlap other intervals in many ways. A location database has been used for all well‐studied experimental organisms. Principles for a human genome database may be derived from this experience.
Antigenic analysis of the major human phosphoglucomutase isozymes:PGM1, PGM2, PGM3 and PGM4
Authors: Drago G. A. , Hopkinson D. A. , Westwood S. A. , Whitehouse D. B.
Published: September 2007

The cross‐reactivity of human phosphoglucomutase isozymes (PGMl, PGM2, PGMS and PGM4) has been investigated using anti‐rabbit muscle PGM polyclonal antibodies. Significant differepces were revealed: an IgG fraction of the antiserum reacted with the primary and secondary PGMl isozymes of all the common phenotypes. However, there was no reaction with the PGM2 or PGM3 isozymes; thus these latter isozymes share no major antigenic determinants with human or rabbit PGMl and are therefore structurally distinct. In contrast, the PGM isozymes of human milk attributed to a fourth locus, PGM4, showed similar cross‐reactivity as PGMl suggesting close structural similarity. The IgG was also employed as a'reagent to remove PGMl from haemolysates so as to allow the unambiguous assessment of the PGMS isozyme patterns by isoelectric focusing. However, no proven genetic variation was encountered in a sample of 32 individuals.
The gene for human neurone specific ubiquitin C‐terminal hydrolase(UCHLl, PGP9.5) maps to chromosome 4p14
Authors: Edwards Y. H. , Fox M. F. , Povey S. , Hinks L. J. , Thompson R. J. , Day I. N. M.
Published: September 2007

Ubiquitin carboxy terminal hydrolase 1, UCHLl, is a neurone‐specific protein involved in theubiquitin‐mediated proteolytic pathway. The gene for human UCHLl has been mapped to

chromosome 4 using the polymerase chain reaction to amplify specifically the human UCHLl sequences in rodent/human somatic cell hybrid DNA. A regional assignment of this locus to

4p14 has been made by in situ hybridization to metaphase chromosomes using both tritium andfluorescently labelled probes.
Genetic epidemiology of ovarian cancer: segregation analysis
Authors: Houlston R. S. , Collins A. , Slack J. , Campbell S. , Collins W. P. , Whitehead M. I. , Morton N. E.
Published: September 2007

The genetic epidemiology of ovarian cancer has been investigated by complex segregationanalysis of 462 pedigrees ascertained through a normal consultand. The observed pattern of ovarian cancer is compatible with an autosomal dominant gene. The gene frequency of the abhormal allele is 0–0015‐0‐0026 with a lifetime penetrance of 0.744.79. The gene frequency accounts for a significant proportion of ovarian cancer in young women. By age 70 the majority of affected women are phenocopies. The results from this analysis should enable the risks of ovarian cancer to be more accurately estimated than by empiric methods forrelatives of affected women, and can maximize the usefulness of screening programmes and future linkage studies.
Genetic epidemiology of complex phenotypes
Authors: Morton N. E. , Shields D. C. , Collins A.
Published: September 2007

A theory is given for complex phenotypes represented by an ordered polychotomy separately for affected (as severity) and for normals (as diathesis), with consideration of history, ascertainment, sampling frames, and phenotype systems. Nonrandom selection of probands by severity is permitted. Both probit and logistic models are developed in a form compatible with segregation and/or linkage analysis. Probabilities are set out in detail in the Appendix. This approach avoids problems that have been encountered with quantitative traits and correlated phenotypes, although using this information.