bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic risks for familial reciprocal translocations with special emphasis on those leading to 9p, 10p and 12p trisomies
Authors: STENE J. , STENGEL‐RUTKOWSKI S.
Published: September 2007

An analysis of genetic risks for reciprocal translocations is given. Data from translocation families, ascertained through unbalanced offspring with trisomy 9p, 10p and 12p, were taken from the literature. The translocations were specified according to (1) the type of trisomy, (2) the degree of resulting chromosomal imbalance (partial short arm trisomies, complete short arm trisomies, complete short arm trisomies including long arm segments) and (3) the type of disjunction (2:2 or 3:1) and segregation (adjacent‐1, adjacent‐2; tertiary trisomy, interchange trisomy). The risks for unbalanced liveborn offspring were high for translocations leading to partial short arm trisomies through 2:2 disjunction and adjacent‐1 segregation (25–29%). They were lower for translocations leading to complete short arm trisomies through the same disjunction/segregation mechanism (5–17 %). Low risks were obtained for translocations, leading through 3:1 disjunction to unbalanced offspring (about 2 %). For 2:2 disjunction and adjacent‐2 segregation and for 3:1 disjunction the risk is significantly lower for male than for female carriers. ‐ The frequency of balanced karyotypes compared with normal karyotypes deviated among the phenotypically normal offspring of parental carriers from the theoretical 1:1 ratio, both for translocations ascertained through trisomy 12p and trisomy 10p.– It was demonstrated that the genetic risk for reciprocal translocations depends exclusively on (1) the degree of possibly resulting genetic imbalance and (2) the probability of the disjunction/segregation mechanism leading to this type of imbalance. Both factors can be predicted from position of breakpoints. – The precision of breakpoint localizations and its impact on the risk estimation are also considered. — Finally, general rules for genetic counselling of families with reciprocal translocations are indicated.
Genetic studies on hydatidiform moles II. The origin of complete moles
Authors: LAWLER S. D. , POVEY S. , FISHER R. A. , PICKTHALL V. J.
Published: September 2007

An investigation of 50 histologically complete hydatidiform moles was by examining the molar tissue after termination of pregnancy. Attempts were made to study chromosomes and 11 polymorphic enzymes in the moles and in the blood of the patient and her spouse, although not all studies were possible on every case. Useful information about the origin of the mole was obtained in 28 cases. In no case was there evidence of a maternal contribution and in 14 cases a maternal contribution was definitely excluded. In 27 cases, including the 5 tested who have subsequently required treatment, the mole was homozygous for all genetic markers examined. There were 32 examples, arising in 21 moles, of loci homozygous in the mole where the male parent was known to be homozygous. There was a single example of a mole heterozygous at one proximal locus (PGM3).

The findings are in favour of the doubling of a haploid genome as the most likely origin of the vast majority of complete moles.
Human triploidy: relationship between parental origin of the additional haploid complement and development of partial hydatidiform mole
Authors: JACOBS P. A. , SZULMAN A. E. , FUNKHOUSER J. , MATSUURA J. S. , WILSON C. C.
Published: September 2007

One hundred and six triploids were ascertained during a study of 1500 consecutive spontaneous abortions. The mechanism of origin of the additional haploid complement was investigated by comparing parental and foetal cytogenetic heteromorphisms and a histopathological examination of each triploid was done in a subsequent blind study.

The mechanism of origin of the additional haploid complement was found to be highly correlated with the development of partial hydatidiform mole and with gestational age. All 51 paternally derived triploids in which a pathologic diagnosis could be made were partial moles, whereas only 3 of 15 maternally derived triploids on which a diagnosis could be made were molar. The mean gestational age of the paternally derived triploids was 122 days while that of the maternally derived triploids was only 74 days.

It was suggested that the development of partial mole was primarily associated with the presence of two paternal haploid chromosome complements, the association with relatively long gestational ages being a secondary one consequent upon retention of the molar placentae for many weeks after foetal demise.
Chiasma derived genetic lengths and recombination fractions: chromosomes 2 and 9
Authors: LAURIE D. A. , PALMER R. W. , HULTÉN M. A.
Published: September 2007

An investigation of chiasma distribution in chromosomes 1, 2 and 9 in the human male has shown that each arm consistently has a characteristic and highly non‐random distribution of recombination. The chiasma frequencies of chromosome regions corresponding to the major mitotic bands have been used to construct genetic maps under the assumption that there is no chromatid interference or chiasma movement and no difference between meiotic and mitotic band positions. This paper presents genetic lengths and recombination fractions for these bands and for combinations of bands in chromosomes 2 and 9. Our results are particularly useful for relating genetic distance to recombination fraction and for dealing with long stretches of chromosome which cannot easily be analysed by any other techniques.
Exploration and mating range in African Pygmies
Authors: CAVALLI‐SFORZA L. L. , HEWLETT B.
Published: September 2007

The distributions of exploration range and of mating range were studied among Aka Pygmies of the Central African Republic. Exploration range is defined and methods of estimation for single individuals suggested. A simple exponential distribution is found for individual Aka Pygmies, with variation of exploration range (the parameter defining mobility) with sex, age and ethnic affiliation. Distribution of distances from birthplace and place of residence are compared and show modest differences. The frequency of visits to a given place has also been studied.

The average distance between birthplaces of mates is very similar to the mean exploration range. Correlations between individual exploration and mating ranges suggest that it is the male who may be choosing a marriage partner among Pygmies. A theory by Boyce, Küchemann & Harrison (1967) on the relations between ‘neighbourhood knowledge’ and mating distance is inapplicable because of its reliance on the Pareto distribution, which does not apply in the present case, and of other unnecessary assumptions, but the general priciple of a close relationship between exploratory activity and mating distance seems valid, at least in the present case. Suggestions are made for causes of the difference between the present distributions and those with other shapes observed in less primitive economies.
A description of human aromatic α‐keto acid reductase
Authors: DONALD L. J.
Published: September 2007

A reductase specific for aromatic α‐keto acids (KAR) is described. It is found in several human tissues, including red cell lysates and fibroblasts. In a population survey, one of 110 red cell lysates tested had a three banded isozyme pattern; this suggests that the enzyme has a dimeric structure and that its locus may be polymorphic. Analysis of KAR isozymes in a series of human/Chinese hamster somatic cell hybrids also indicated that the active enzyme has two subunits coded by a gene on human chromosome 12, probably very close to LDHB.
A genetic characterization of the human diaphorase‐4 deficiency
Authors: EDWARDS Y. H. , HOPKINSON D. A. , CARRITT B.
Published: September 2007

Analyses of DIA4 activity in cultured cells from a random population, a small family and human/rodent somatic cell hybrids support the view that the quantitative polymorphism of human DIA4 can be attributed to the segregation of a ‘low activity’ allele.

(1) In a series of lymphoblastoid cell lines from 52 unrelated individuals, three lines were found which did not exhibit DIA4 after electrophoresis and showed low levels of NADPH diaphorase activity. The frequency (6%) of the DIA4 ‘absent’ phenotype is close to that (4%) determined previously by analysis of post‐mortem tissue.

(2) Cultured fibroblasts from a small family in which the DIA 4 low‐activity allele was apparently segregating were analysed. The NADPH diaphorase activity of the propositus (DIA4 ‘absent’ phenotype) was very low (less than 6% of normal). He also exhibited very weak DIA4 isozymes of unusual electrophoretic mobility. The activity of both parents and sib was about half the normal level, suggesting that these individuals are heterozygous for the low‐activity allele.

(3) Analysis of a series of independent human/hamster hybrid clones, made using a human parent heterozygous for phosphoglycolate phosphatase (PGP) and DIA4, suggested that in this particular individual the DIA 4 low‐activity allele segregates with the PGP 2 allele. However, there were 2 hybrids amongst a total of 16 which gave discordant results and these are to be the subject of further analysis by subcloning.
A recursive algorithm for inferring gene origins
Authors: THOMPSON E. A.
Published: September 2007

Kidd et al. (1980) studied the allelic origins of a recessive trait in an extensive and complex genealogy. Due to computational limitations, the hypotheses they could consider were limited, and the dependencies in descent from alternative ancestors and to different sibships were not considered. Karigl (1981) developed a recursive algorithm for the computation of multiple kinship coefficients. Here we show that very similar algorithms apply to probabilities of the joint descent of multiple genes from specified ancestral genes. This makes possible a far more extensive analysis of hypotheses of allelic origins in a genealogy.
HLA sharing in multiplex sibships
Authors: SUAREZ B. K. , CROUSE J. , EERDEWEGH P. VAN
Published: September 2007

For an arbitrary number of affected sibs with unaffected parents, the proportion that share both marker haplotypes identical by descent is derived for the generalized single locus model. This proportion is shown to depend on the underlying parameters of the disease transmission model, on the total sibship size and on the number of sibs who are affected. The variety of identity by descent patterns suggests that any attempt to infer the presence of other independent disease susceptibility loci solely on the basis of an observed inverse relationship between the degree of haplotype sharing and the number of affected sibs, is liable to result in spurious conclusions.
Relationship between levels of biochemical heterozygosity and morphological variability in human populations
Authors: KOBYLIANSKY E. , LIVSHITS G.
Published: September 2007

The relationships between the heterozygosity of the loci of biochemical and morphological traits were compared in seven Jewish populations. This comparison was based, on the one hand, on the average heterozygosity of seven biochemical loci (four blood group and two enzymatic ones) and, on the other hand, on five morphological characters. To assess the heterozygosity level for quantitative traits (normal distribution), we found it useful to measure h = CVμ, where CV is the coefficient of variation, and μ is the deviation of the population mean from the general average divided by the standard deviation of the general distribution. Actually, ‘h’ represents an inverse measure of the heterozygosity. Marked negative correlation was detected between the biochemical and morphological heterozygosity. This negative correlation was attributed to the convergent influence of inbreeding on different loci, but other possible mechanisms are discussed.
A genetic polymorphism of a human urinary mucin
Authors: KARLSSON S. , SWALLOW D. M. , GRIFFITHS B. , CORNEY G. , HOPKINSON D. A. , DAWNAY A. , CARTRON J. P.
Published: September 2007

We report here a novel genetically determined polymorphism of a human urinary mucin which is demonstrable by the separation technique of SDS polyacrylamide gel electrophoresis, followed by detection with radio‐iodinated lectins. The mucins are demonstrable using various lectins but the polymorphism is most easily recognized using peanut agglutinin and we therefore propose to designate this new genetic locus PUM (peanut‐reactive urinary mucin). Four common alleles have been identified and an autosomal codominant mode of inheritance has been found in the families studied so far.
Surnames in Sardinia
Authors: ZEI G. , MATESSI R. GUGLIELMINO , SIRI E. , MORONI A. , CAVALLI‐SFORZA L.
Published: September 2007

1. Distributions of surnames were examined using data from about 40000 individuals from consanguineous marriages (1930‐59) in the island of Sardinia. They fit the Karlin‐McGregor (1967) distribution for neutral alleles.

2. The logarithmic distribution by Fisher (1943) and the Karlin‐McGregor (1967) distribution give practically indistinguishable fits to these data.

3. The two parameters underlying the Fisher distribution, a and v, are fully interdependent, given the sample size N. From the latter and from the number of surnames S, they can be easily and satisfactorily estimated.

4. The quantity a measures immigration to the area and can be taken as a measure of the richness of the gene pool, being closely related to the quantity θ=Neμ (Ne= effective population size, μ= mutation rate) after the necessary corrections have been taken care of.

5. Surnames behave like genes transmitted by the male line. Differences of female and male migrations require correction for comparison with data from autosomal gene frequencies but there seem to be no important differences between female and male migration in this area, as judged by analysis of pedigrees of consanguineous marriages.

6. It is probable that the migration estimates obtained in this material are lower than real ones, mostly because of a bias characteristic of the particular source of surnames here employed.

7. The distribution of surnames from areas which have very recently undergone economic development is not at equilibrium and is not fitted as well as that of areas which have had less important recent changes. As might be expected, the disturbance is particularly marked in the class most sensitive to effects of recent increases in migration, that of rarest surnames (represented by only one individual). In fact in this material it is noticeable only in this class and correction can be made for it.

8. At equilibrium of migration and drift, the number of surnames in a population sample of given size can give a complete description of the population structure for that sample, in the same sense that the number of alleles is a sufficient statistic for the study of neutral evolution. The study of surnames, given their nature of ‘neutral’ alleles, the large number of alleles and the ease with which large numbers of individual data can be collected, can be a valuable help in the study of genetic population structure.
DNA analysis in patients with hereditary fructose intolerance
Authors: Grégori C. , Besmond C. , Odievre M. , Kahn A. , Dreyfus J. C.
Published: September 2007

Restriction fragments of the adlolase B gene were studied in 11 patients with hereditary fructose intolerance and compared with the normal pattern. No major deletion of the gene was observed. One patient was found to be a compound heterozygote since one allele with normal restriction sites was inherited from the mother and the other with an abnormal Barn HI site was inherited from the father. The anomaly of the Barn HI fragment observed in this family was not found in 62 normal controls from the same origin as the patient.
Parental age and unbalanced Robertsonian translocations associated with Down syndrome and Patau syndrome: comparison with maternal and paternal age effects for 47, + 21 and 47, + 13
Authors: Hook E. B.
Published: September 2007

Data are analysed on livebirths with trisomic syndromes associated with unbalanced Robertsonian translocations born from 1968 to 1981 and reported to the New York State Chromosome Registry. The maternal ages of reported cases were compared with those of the livebirths in the general population who were born in the same year. The number of translocations studied, the mean case‐control differences in years in maternal age (and the standard errors of the mean) were respectively, as follows:

D/21 mutants, n= 36. – 0·1 (±0·9); G/21 mutants, n= 46, + 1·5 (±0·8); D/13 mutants, n= 16, + 0·6 (± 1·5); D/21 inherited, n= 12, – 1·0 (± 1·4); G/21 inherited, n= 3, – 0·3 (± 4·4); and D/13 inherited, n= 6, + 2·1 (± 2·4).

There was little change in any category if the few cases diagnosed prenatally were included. Only the value for the G/21 mutants is significantly different from zero at the 0·05 level. (The results on G/21 mutants in maternal age are consistent with an earlier Japanese report of an increase of about 2 years over the control values.) The distribution of maternal ages suggests that G/21 mutants may be produced both by maternal age‐independent, and maternal age‐dependent components. The data on D/21 mutants, however, do not indicate the negative association with maternal age reported in Japan. Differences between this study and the Japanese study in analyses of controls may explain this slight variation. But in any event both studies reveal no evidence for an increase in maternal age for unbalanced D/21 mutant or D/21 inherited translocations associated with Down syndrome. This is evidence against the hypothesis that relaxed selection during gestation, after recognition of pregnancy, accounts for the maternal age effects of 47, + 21. In comparison with the results on Robertsonian translocations, the case‐control differences in maternal age in years (and the standard errors of the mean) for 47. + 21 for 2148 livebirths was + 4·6 (± 0·2), and for 2354 cases including those diagnosed prenatally was + 5·3 (± 0·2). The most likely value for an estimated total of 2292 cases of 47, + 21 livebirths that would have been reported in the absence of prenatal diagnosis was + 5·1 (± 0·2). For 47, + 13, for 98 livebirths the mean case‐control difference in maternal age in years was + 1·5 (± 0·7) and for 116 cases including those diagnosed prenatally was + 3·2 (± 0·7). The most likely value for an estimated 108 cases of 47, + 13 in the absence of prenatal diagnosis was + 1·7 (± 0·6). The data on 47, + 13 livebirths confirm suggestive trends from earlier studies at prenatal diagnosis that the maternal age association of this trisomy is weaker than for 47, + 21 or 47, + 18. With regard to paternal age effects, there was no evidence for case‐control differences in paternal age (after controlling on maternal age as well as year of birth) for any category of defect analysed.
Mutation and selection in the marker (X) syndrome A hypothesis
Authors: Vogel F.
Published: September 2007

Sherman et at. (1984) concluded from a cytogenetic and genetic analysis of families with the marker (X) syndrome that the rate of the mutation leading to this syndrome is extraordinarily high (7×2 times 10–4 in male germ cells), and that these mutations occur exclusively in male germ cells. It is shown by some model calculations that the empirical evidence can be reconciled with more conventional assumptions on the mutation rate if a moderately increased fertility of clinically unaffected female and possibly male carriers in the past is assumed. Indirect evidence for such an increased fertility can be derived from old reports on higher reproduction of slightly subnormal individuals. On the other hand, complete compensation of gene loss in affected individuals by higher fertility of unaffected carriers appears to be rather unlikely. At present, a moderately high mutation rate – as found, for example, in Duchenne muscular dystrophy or haemophilia A – in combination with a moderately increased fertility of clinically unaffected carriers is the most likely alternative.
Review
Authors: Burgoyne P.
Published: September 2007

Book reviews in this articles

Cytogrnetics of the Mammalian X Chromosome. Progress and Topics in Cytogenetics.
Linkage studies in Menkes' disease The Xg blood group system and C‐banding of the X chromosome
Authors: HORN N. , STENE J. , MÓLLEKAER A.‐M. , FRIEDRICH U.
Published: September 2007

Menkes' disease is a rare, genetically determined disturbance of copper metabolism which is transmitted as an X‐linked recessive character. By comparative gene mapping it can be suggested that the most likely localization of the gene for Menkes' disease is on the long arm of the human X chromosome close to band q l3. This regional assignment is supported by the present analysis of the genetic relationship between the Menkes locus, the Xg locus, and the centromere in five Danish families. The evidence suggests close linkage between the Menkes locus and the centromere. The most likely value of the recombination fraction is 0·05 and the maximum lod score is above the conventional +3 limit. Linkage analysis of the Menkes locus and the Xg locus showed a recombination value of 0·24, but the maximum conditional lod score is 0·28, which is far below the conventional +3 limit. The present study demonstrates a successful application of a chromosomal morphological marker in linkage analysis and carrier detection of a single gene disorder. The close linkage between the gene for Menkes' disease and the centromere region was used to improve the classification of several females in whom the copper uptake into cultured fibroblasts was either inconclusive or not available.
β‐Adrenoceptor binding defects in cell lines from families with manic‐depressive disorder
Authors: WRIGHT A. F. , CRICHTON D. N. , LOUDON J. B. , MORTEN J. E. N. , STEEL C. M.
Published: September 2007

Binding of 125I‐iodohydroxybenzylpindolol to β‐adrenoceptors has been examined in lymphoblastoid cell lines from members of 5 families affected by manic‐depressive disorder. Cell lines from 6 manic‐depressives, 7 unaffected relatives and 11 non‐psychiatric controls were examined. Binding was reduced to less than half of control values in cell lines from 4 out of 6 manic‐depressives and only 1 out of 18 unaffected relatives or controls. All the cell lines with reduced β‐adrenoceptor binding came from 3 families; members of the remaining 2 families showed normal binding. These findings suggest that genetic heterogeneity is present in manic‐depressive disorder and that a β‐adrenoceptor defect may influence genetic susceptibility to the disorder.
Tay–Sachs disease and the role of reproductive compensation in the maintenance of ethnic variations in the incidence of autosomal recessive disease
Authors: KOESLAG J. H. , SCHACH S. R.
Published: September 2007

Several deleterious and lethal autosomal recessive genes appear to exist in equilibrium with their normal alleles at a variety of stable, or near stable frequencies of considerable antiquity. One person in 25 is, for instance, a carrier of the Tay‐Sachs gene among Ashkenazi Jews, compared with 1 in 300 among Sephardic and Oriental Jews and non‐Jews. The explanations offered for t his phenomenon have generally not been entirely satisfactory.

It has been shown that parents replace fortuitous infant and childhood deaths with, on average, approximately two surviving sibs each. When mutation rates are low, this practice, which has also been shown to occur among other animals, can maintain considerable variations in the stable incidence of autosomal recessive disease, should such ethnic polymorphism arise through genetic drift, the founder effect or hitch‐hiking. High mutation rates would appear to preclude ethnic variations in the stable incidence of genetic disease.
Mapping of the gene coding for the human GM2 activator protein to chromosome 5
Authors: BURG J. , CONZELMANN E. , SANDHOFF K. , SOLOMON E. , SWALLOW D. M.
Published: September 2007

The gene coding for the GM2 activator protein has been mapped to human chromosome 5, using an enzyme‐linked immunoadsorbant assay (ELISA) to identify the human protein in human‐mouse somatic cell hybrids.
Genetic and population structure of four Sardinian villages
Authors: PIAZZA A. , MAYR W. R. , CONTU L. , AMOROSO A. , BORELLI I. , CURTONI E. S. , MARCELLO C. , MORONI A. , OLIVETTI E. , RICHIARDI P. , CEPPELLINI R.
Published: September 2007

1. Data on microgeographic population structure on four neighbouring villages of Sardinia island (Italy) are presented and discussed.

2. Two villages are located in the lowlands where malaria from Plasmodium falciparum was endemic until the eradication of paludism. The other two villages are located in the highlands and they were malaria‐free because of the altitude.

3. Census data, inbreeding, migration matrices and surname distributions have been collected. The genetic differentiation of the four villages, tested for 31 genetic polymorphisms (106 alleles), is only in part compatible with migration rates inferred from demographic data.

4. The possible adaptive nature of some genetic markers with respect to malarial resistance is discussed. Ambiguous results from population genetics quantitative methods do not support definite answers.
Differences in methylation on the active and inactive human X chromosomes
Authors: LINDSAY S. , MONK M. , HOLLIDAY R. , HUSCHTSCHA L. , DAVIES K. E. , RIGGS A. D. , FLAVELL R. A.
Published: September 2007

Methylation of CCGG sites was examined in four regions of the X chromosome with four X‐chromosome clones, three obtained by cloning random segments and one encoding a structural gene. In DNA from human peripheral blood cells unmethylated sites correlating with the inactive X chromosome were detected in the vicinity of two of the random clones and also in the vicinity of a cloned sequence of the X‐linked phosphoglycerate kinase gene (PGK). The third random clone covered a region whose methylation pattern was unchanged between the active and inactive X chromosomes. Differential methylation at the sites detected appears to have no functional role in the maintenance of the inactive X chromosome since both active and inactive X chromosomes were found to be undermethylated in DNA from human lymphoblastoid cells.
Linkage between the loci for peptidase D and apolipoprotein CII on chromosome 19
Authors: BALL S. P. , DONALD J. A. , CORNEY G. , HUMPHRIES S. E.
Published: September 2007

Families segregating for PEPD were investigated for linkage between PEPD and APOC2. The results provide evidence for close linkage between PEPD and APOC2 in males.
Localization of the oncogene c‐erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17
Authors: SHEER D. , SHEPPARD D. M. , BEAU M. le , ROWLEY J. D. , ROMAN C. SAN , SOLOMON E.
Published: September 2007

Using in situ hybridization, c‐erb A1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46, XX, t(15;17)(q22;q11). Previous work has shown that c‐erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12–21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12–21.
A genetic map of chromosome 19 based on family linkage data
Authors: SHERMAN S. L. , BALL S. P. , ROBSON E. B.
Published: September 2007

A large linkage group has been assigned to chromosome 19. The loci have been ordered using a two‐point mapping analysis based on all available family linkage data summarized in the form of lod score tables.
Further studies on bivalent chiasma frequency in human males with normal karyotypes
Authors: LAURIE D. A. , HULTÉN M. A.
Published: September 2007

Previously unpublished data on the chiasma frequency of individual bivalents identified by a triple staining technique are presented for four males. The total autosomal cell chiasma frequency and sex chromosome univalence frequency are also given for these males and for three others. All seven males had apparently normal 46, XY karyotypes and normal spermatogenesis. The extent of inter‐individual variation in cell and bivalent chiasma frequency and the gross relationship between chromosome length and chiasma frequency are discussed.
Human L‐xylulose reductase variation: family and population studies
Authors: LANE A. B. , JENKINS T.
Published: September 2007

Only one of the two main l‐xylulose reductases present in human tissue is deficient in individuals with essential pentosuria (Lane, 1985). The isozyme which is affected by the pentosuria mutation occurs as mitochondrial and cytosolic forms in normal individuals, whereas the other isozyme (which is not affected by the mutation) occurs only in the cytosol. A new assay of red cell l‐xylulose reductase activity has facilitated the identification of carriers of the essential pentosuria allele at both family and population levels. Reinvestigation of a Lebanese family in which pentosuria has previously been thought to be dominantly inherited reveals that the condition is recessively inherited in this family as well. A minimum estimate of the frequency of the pentosuria allele in an Ashkenazi‐Jewish population, calculated from the apparent heterozygote frequency, is 0·0127. The likelihood of the Ashkenazi and Lebanese pentosuria alleles being the same is discussed.
On the perpetuation of relic genes having an inviable homozygote
Authors: KOESLAG J. H. , SCHACH S. R.
Published: September 2007

Reproductive compensation may be prezygotic or postzygotic. Prezygotic compensation is the replacement of inviable infants by one or more additional births. When the marital fertility rates are greater than necessary to replace the parents, however, many traditional societies ensured that any surviving progeny in excess of two (on average) did not marry, or married only if they replaced an older sib as heir to the family estate. We call this postzygotic compensation. We show that the coefficient of biologically effective compensation approximates unity when normal and genetic‐disease‐affected sibships were both sufficiently large to ensure that, on average, two or more sibs survived to the end of the reproductive period, irrespective of the level of prezygotic compensation. The impact of these types of compensation on the population genetics of Tay‐Sachs disease and cystic fibrosis is discussed.
Males, Females and Hermaphrodites
Authors: Mittwoch Professor Ursula
Published: September 2007

Ancient myths of an hermaphrodite origin of man and his subsequent bisection into male and female individuals receive unexpected confirmation from the embryological evidence. The genital ridge contains the components to form either a testis or an ovary, while two sets of genital ducts are the forerunners of the male and female reproductive tracts. The presence of potentially hermaphrodite rudiments in different organisms resulted in the failure of attempts to formulate the determination of sex in terms of classical genetics. This, in turn, has led to the hypothesis that the function of the mammalian Y chromosome is to enhance the growth of the gonadal rudiment in male embryos. The hypothesis provides an explanation for the observed bilateral asymmetry of gonadal differentiation in human hermaphrodites in terms of the bilateral asymmetry of growth of human fetal gonads. The human condition can be related to the marked asymmetry of gonadal growth and differentiation in birds. The effect of temperature in the determination of sex in alligators has likewise been explained in terms of gonadal growth. The variety of sex‐determining mechanisms met with in vertebrates suggests a non‐sex‐specific effect adapted to specific biological needs. It is suggested that certain DNA sequences on the human Y chromosome act by enhancing the growth of somatic cells in the gonadal rudiment, leading to precocious differentiation of the testis.
The human type II collagen gene (COL2A1) assigned to 12q14.3
Authors: LAW M. L. , TUNG L. , MORSE H. G. , BERGER R. , JONES C. , CHEAH K.S.E. , SOLOMON E.
Published: September 2007

A cosmid clone containing the entire human type II α1 collagen gene (COL2A1) was used as probe in the Southern analysis of DNA from a panel of human/hamster somatic cell hybrids containing different portions of human chromosome 12. Two of the hybrids exhibited a similar terminal deletion q14.3→qter, but one was positive for the gene while the other was negative. Therefore, the gene must reside in the region q14.3.
The C8A and C8B loci are closely linked on chromosome 1
Authors: ROGDE S. , OLAISEN B. , GEDDE‐DAHL T. , TEISBERG P.
Published: September 2007

Close linkage was demonstrated between the loci governing the polymorphisms of complement component C8 α‐γ (C8A) and β (C8B). Both C8 loci were linked to the chromosome 1 marker loci PGM1 and Rh. The distance between the two C8 loci and PGM1 appeared identical in males and females. A female/male ratio of 1.6 was observed between the two C8 loci and Rh. No evidence for linkage between the C8 loci and Fy was found. Preliminary results of this study were presented at the Eighth International Workshop on Human Gene Mapping, Helsinki, August 1985 (Rogde et al. 1985b).
Chi‐squared tests with small numbers
Authors: SMITH C. A. B.
Published: September 2007

The usual advice given in standard texts is to combine classes when expected numbers are too small. It is suggested that an alternative would be to use the exact values of teh mean and variance of χ2, for which algebraic expressions are provided. The reliability of the test can be improved by using √χ2 instead of χ2 as the test criterion.
Secular trend of twin concordance in late fetal death
Authors: TERRENATO L. , NOVELLETTO A.
Published: September 2007

In the present paper the secular trend of twin concordance for late fetal death rate has been analysed. The results show that, while the correlation remains unchanged in MZ twins, it is greatly reduced in DZ twins. This renders untenable the assumption of comparable secular trends in the intrauterine environment of the two types of twins. An appropriate model is given for the estimation of the environmental (intrauterine) factors in late fetal death concordance, under the assumption of a wide range of frequencies for unconditional lethals.
Genetic polymorphism and fertility parameters in the Aymara of Chile and Bolivia
Authors: CHAKRABORTY R. , FERRELL R. E. , BARTON S. A. , SCHULL W. J.
Published: September 2007

To determine whether increased fitness in natural populations is associated with heterozygosity, several studies have attempted to correlate heterozygosity at one or a few genetic loci with fitness‐related quantitative traits. The results have been equivocal at best. Furthermore, data on fertility‐related parameters and the extent of genetic polymorphism at a large number of loci in man are quite scanty. This report examines the association of four fertility‐related parameters (number of pregnancies, number of livebirths, number of children surviving at least one year and number of children alive at the time of the survey) with heterozygosity at 17 polymorphic immunological and biochemical systems in the Aymara of Chile and Bolivia. Women 45 years of age and above, on whom complete fertility histories and phenotype data are available, were included in the study (n=190). None of the fertility parameters seem to be correlated with heterozygosity, as measured by the proportion of polymorphic loci. For some individual loci, however, an association between heterozygous state and fertility parameters exists. Even in these cases, heterozygosity did not always confer higher fertility. To see whether these negative results are due to heterogeneity in the data, the total sample was divided according to altitude of residence and ethnicity. The conclusions remained the same, indicating that the lack of association of these fertility parameters with genetic polymorphism is not due to population heterogeneity alone. Reproductive fitness differentials, therefore, were not detectable in the Aymara by heterozygosity determined by the polymorphic genetic systems scored by serological and electrophoretic techniques.
The association of HLA‐linked genes with systemic lupus erythematosus
Authors: GREEN J. R. , MONTASSER M. , WOODROW J. C.
Published: September 2007

The reported associations between HLA antigen DR3 and null (QO) alleles at the C4A and C4B loci and systemic lupus erythematosus are here analysed. The empirical logistic method has been applied to a body of data which included the relevant genotypes. The analysis suggests that the association with null alleles at the C4 loci is primary and the DR3 association is likely to be secondary to this. This may give information as to the location of the HLA‐linked disease susceptibility gene.
Localization of MIC5 to the region between HPRT and G6PD on the human X chromosome
Authors: HOPE By R. , GOSS S. , SOLOMON E. , ROPERS H.‐H. , BANTING G. , GOODFELLOW P. N.
Published: September 2007

The X‐linked gene, MIC5, encodes a human cell‐surface antigen, R1. We have assigned MIC5 to the region between HPRT and G6PD on the long arm of the X chromosome. Regional localization was based on the pattern of reactivity of the R1 monoclonal antibody with human‐rodent somatic cell hybrids which contained different fragments of the human X chromosome.
Linkage between the loci for peptidase D and cytochrome P‐450 (CYP1) on chromosome 19
Authors: DAVIS By M. B.
Published: September 2007

Families segregating for PEPD have been investigated for linkage between PEPD and CYP1. The results provide evidence for close linkage between PEPD and CYP1 in males.
Expected genetic drift and observed gene variation in a small isolated human population
Authors: PRESCIUTTINI S.
Published: September 2007

Data on the gene frequencies of four blood groups and six polymorphic erythrocyte enzymes were collected in a small population of the Northern Apennines (municipality of Zeri, Tuscany, Italy), whose civic records are available from 1866 on. Starting from the assumption that the mean gene frequencies of large populations of the neighbouring regions may represent a good estimate of the frequencies of the ‘mother population’ of the isolate, an observed value of the standardized (‘Wahlund’) variance of gene frequencies was computed and found to be 0·0131. The expected value of the same variance, due to random drift, has been computed on the basis of an evaluation of the immigration to the isolate, drawn from the marriage register of the municipality: this value was 0·0103.
Chromosomal assignment of the gene encoding the human tissue inhibitor of metalloproteinases to Xp11.1–p11.4
Authors: SPURR N. K. , GOODFELLOW P. N. , DOCHERTY A. J. P.
Published: September 2007

The tissue inhibitor of metalloproteinases (TIMP) is thought to play a regulatory role in connective tissues by forming inactive complexes with those metalloproteinases that are normally responsible for connective tissue turnover. The human gene encoding TIMP has been mapped to the X chromosome in the region Xp11. 1–p11.4.
The LW: C3 recombination fraction in female meioses
Authors: LEWIS M. , KAITA H. , PHILIPPS S. , COGHLAN G. , McALPINE P. J. , COOPLAND G. R. , WOODS R. A.
Published: September 2007

No recombinants between LW and C3, using a C3 DNA probe, were observed in 16 female meioses: z 4·216 at θ= 0·00. Combined with the data of Sistonen (1984) the recombination fraction between LW and C3 is estimated to be 0.09 (Ẑ 3·773) in females.
Natural selection associated with birth weight V. The secular relaxation of the stabilizing component
Authors: ULIZZI L. , TERRENATO L.
Published: September 2007

The secular trend of stabilizing selection on birth weight has been studied during the last decades in 17 countries, representative of America, Asia and Europe. A relaxation of the intensity of selection is regularly observed, which can probably be attributed to a progressive reduction of the environmental component of birth weight variance.
The human α2(IV) collagen gene, COL4A2, is syntenic with the α1(IV) gene, COL4A1, on chromosome 13
Authors: SOLOMON E. , HALL V. , KURKINEN M.
Published: September 2007

We have previously assigned the gene for the αl chain of type IV collagen to chromosome 13. In this report we show that the gene coding for the second chain of this heterotrimer is on the same chromosome. This is the first example of the genes for both chains of one collagen molecule being syntenic.
Localization of the oncogene c‐erbA2 to human chromosome 3
Authors: RIDER S. H. , GORMAN P. A. , SHIPLEY J. M. , MOORE G. , VENNSTROM B. , SOLOMON E. , SHEER D.
Published: September 2007

The human c‐erbAl gene has been previously mapped to chromosome 17. We have now mapped c‐erbA2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c‐erbA2 to the chromosome region 3p21‐pter.
Characterization of a panel of highly variable minisatellites cloned from human DNA
Authors: WONG Z. , WILSON V. , PATEL I. , POVEY S. , JEFFREYS A. J.
Published: September 2007

Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem‐repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus‐specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously‐isolated minisatellite designated pΛg3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair‐wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus‐specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered.

We are very grateful to Professor J. Dausset and Dr H. Cann at the Human Polymorphism Study Centre, Paris. for the generous provision of DNA samples from the panel of CEPH families, to Dr Mary Davis for providing DNA from the JDA hybrids, and also to the following people who kindly allowed us to use their hybrids. Dr Ellen Solomon. Dr Nigel Spurr. Dr P. Goodfellow, Dr Denise Sheer, Dr John Cowell and Dr Ben Carritt. We also thank Anabel Kearney who did the enzyme analysis on the hybrids, and Lynne West who did the karyotyping. We are also grateful to the Leicestershire Constabulary for their permission to cite details of the forensic analysis. A.J.J. is a Lister Institute Research Fellow, and this work was supported by a grant to A.J.J. from the Medical Research Council. The minisatellite probes are the subject of Patent Applications, and commercial enquiries should be addressed to the Lister Institute of Preventive Medicine, Brockley Hill, Stanmore. Middlesex, H A7 4JD, U.K.
Frequency and distribution of rare electrophoretic mobility variants in a population of human newborns in Ann Arbor, Michigan
Authors: MOHRENWEISER H. W. , WURZINGER K. H. , NEEL J. V.
Published: September 2007

We have summarized the frequency and distribution of the rare variants encountered during the screening of 258 815 allele products, the products of 51 different loci, in 3242 predominantly Caucasian (88 %) newborns. Seventy‐nine different rare variants, representing 187 occurrences, were identified. Almost 60 % (46 of 79) of the rare variants occurred as singletons while another 20 % were seen in two unrelated individuals. No rare variants were detected at 18 loci while no variants, either rare or polymorphic, were detected at 14 loci. More rare variants were identified at loci that were classified as polymorphic and also at loci where the gene products exist as a monomer. A positive relationship was observed between variant frequency, either classes or copies, and subunit molecular mass.
Diversity of some gene frequencies in European and Asian populations. III. Spatial correlogram analysis
Authors: BARBUJANI G.
Published: September 2007

The gene frequencies at eight loci in some European and Asian human populations have been subjected to spatial autocorrelation analysis, using Geary's c coefficient. Contrary to what is expected for markers affected only by gene flow and genetic drift, the spatial correlograms show distinct modes of gene frequency variation: there are significant clinal patterns (at the GLO and ESD loci), significant non‐clinal patterns (AK, ADA, 6‐PGD and GPT) and marginally significant patterns (PG0P and SGD). Any hypothesis on the evolution of these polymorphisms should account for the observed heterogeneity of their geographical distributions.
Rhodanese isozymes in human tissues
Authors: WHITEHOUSE D. B. , PILZ A. J. , PORTA G. , HOPKINSON D. A.
Published: September 2007

An investigation of a range of tissue homogenates by various electrophoretic methods, followed by staining for specific enzyme activity, has revealed a series of isozymes of human rhodanese. Polyacrylamide gel isoelectric focusing provided the most data and rhodanese activity was found in all of the tissues examined. The simplest isozyme pattern was found in red cell lysates; liver homogenates generated the most complex pattern which included the ‘red cell’ forms together with a set of more basic ‘tissue’ isozymes. Variation in isozyme patterns thought to be attributable to storage changes affecting reactive sulphydryl residues was observed in ‘red cell’ rhodanese but no genetic variants of either ‘red cell’ or ‘tissue’ rhodanese were encountered in a study of material from the European population. We conclude that ‘red cell’ and ‘tissue’ rhodanese are determined by separate genes but more than one locus may be concerned with the synthesis of the heterogeneous ‘tissue’ isozymes.
The assignment of the human gene coding for complement C5 to chromosome 9q22‐9q33.
Authors: JEREMIAH S. J. , WEST L. F. , DAVIS M. , POVEY S. , CARRITT B. , FEY G. H.
Published: September 2007

The presence or absence of the human gene for the fifth component of complement (C5) was analysed in 19 human‐rodent hybrid cell lines by hybridization to a radiolabelled probe derived from a human C5 cDNA clone. The segregation of C5 in these hybrids suggested that the gene is localized on chromosome 9, in the region 9q21‐9qter. In situ hybridization refined the assignment of C5 to chromosome 9q22‐33.
The major phenobarbital‐inducible cytochrome P‐450 gene subfamily (P450IIB) mapped to the long arm of human chromosome 19
Authors: SANTISTEBAN I. , POVEY S. , SHEPHARD E. A. , PHILLIPS I. R.
Published: September 2007

We have recently isolated a cloned cDNA that codes for a human orthologue of the major phenobarbital‐inducible cytochrome P450IIB subfamily of rodents. The cloned human cDNA was used to analyse, by Southern blot hybridization, DNA extracted from a panel of 9 independent human‐rodent somatic cell hybrids. The results indicate that all members of the P450IIB gene subfamily of man are located on chromosome 19. Evidence from hybrids containing different regions of human chromosome 19 localizes this cytochrome P‐450 gene subfamily further to the long arm of chromosome 19 in the region cen‐q13.3. We propose the designation CYP2B for this locus.