bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare phosphoglucomutase phenotypes
Authors: HOPKINSON D. A. , HARRIS HARRY
Published: September 2007

1. PGM phenotypes have been determined by starch‐gel electrophoresis in more than 2000 unrelated ‘ English’ people and several smaller samples from other populations.

2. Besides the three common phenotypes (PGM 1, 2–1 and 2), eleven rare phenotypes have been identified, and their genetical basis investigated.

3. Nine of the new phenotypes, PGM 3–1, 3–2, 4–1, 4–2, 5–2, 6–1, 6–2, 7–1 and 7–2, appear to represent heterozygous combinations of one or another of a series of rare alleles, PGM31, PGM41, PGM51, PGM61 and PGM71, with either PGM11 or PGM21. Each of these alleles probably determines the formation of two new isoenzyme components which are homologous with components a and c determined by PGM11 and components b and d determined by PGM21.

4. The ‘Atkinson’ and ‘Palmer’ phenotypes are thought to represent heterozygotes for alleles at a different locus, PGM2. The common allele at this locus is designated PGM12 and the postulated genotype for the ‘Atkinson’ phenotype is PGM12PGM22 and for the ‘Palmer’ pheno‐type is POM12PGM32. It is suggested that PGM12 determines isoenzyme components e, f and g and that PGM22 and PGM32 each determine three isoenzyme components which are electrophoretically different from but homologous with e, f and g.

5. The ‘Atkinson’ phenotype appears to have an appreciable incidence in Negro populations and has so far not been observed in any non‐Negro group.
Linkage scores and corrections in simple two‐ and three‐generation families
Authors: SMITH CEDRIC A. B.
Published: September 2007

The theory of the method of z‐scores and corrections is discussed. The reasons for their use are explained, and their theoretical justification. Formulae are given for the cases of X‐linked genes and double backcross autosomal matings. New tables of the scores are also provided.
Natural selection and the de Finetti diagram
Authors: CANNINGS C. , EDWARDS A. W. F.
Published: September 2007

The properties of the de Finetti diagram for the case of two alleles at a locus are described in terms of homogeneous co‐ordinates.
Heritability of liability and concordance in monozygous twins
Authors: SMITH CHARLES
Published: September 2007

Results from heritability of liability model of Falconer (1965) have been revised, eliminating two sources of bias. The results have been graphed for convenient usage, and in the absence of environmental similarities among relatives can apply to all kind of relatives. Confidence levels for the heritability (or correlation) estimates can also be read directly off the graph.

The results also apply to concordance rates in MZ twins. They show that, in the absence of environmental similarities, concordance rates for a disease in MZ twins will only be high if the heritability is very high. Thus a low concordance rate in MZ twins cannot be taken to prove that genetic factors are not important in the predisposition to a disease.
Molecular size estimates of the human phosphoglucomutase isozymes by gel filtration chromatography
Authors: McALPINE PHYLLIS J. , HOPKINSON D. A. , HARRIS HARRY
Published: September 2007

1. Molecular sizes of the three sets of the human phosphoglucomutase isozymes attributable to the loci PGM1, PGM2 and PGM3 have been studied by gel nitration.

2. The PGM2 isozymes (M.W. C. 61,000) appear to be significantly larger than the PGM1 and PGM3 isozymes and the PGM3 isozymes (M.W. C. 53,000) appear to be slightly larger than the PGM1 isozymes (M.W. C. 51,000).

3. No inter‐allelic or intra‐allelic differences in molecular size were detected.

4. The estimated molecular size for rabbit muscle PGM by the same method is similar to that obtained for the human PGM1 isozymes. This is somewhat lower than previously reported estimates obtained by ultra centrifugation.
Analysis of population structure
Authors: MARUYAMA TAKEO
Published: September 2007

Stepping stone model of population structure was analysed in one‐dimensional eases of finite length, with special reference to variance and correlation of gene frequencies between colonies. Two types of migration patterns at boundarjr colony were treated. Explicit formulas for the variance and the correlation were obtained. In order to check the validity of the analytical results, several Monte Carlo experiments were performed by computer. Some extensions of the analyses were also given.
Fluorescent evidence for spermatocytes with two Y chromosomes in an XYY male
Authors: HULTÉN MAJ , PEARSON P. L.
Published: September 2007

A quinacrine fluorescent technique has been used to identify the presence and frequency of Y chromosomes at different stages of spermatogenesis in &n XYY male. Forty‐five per cent of primary spermatocytes contained two Y chromosomes associated as a YY bivalent, and the patient exhibited an increased frequency of YY bearing spermatozoa as compared to three control males.
The incidence of triplets and higher multiple births in some rural and urban populations in Western Nigeria
Authors: NYLANDER P. P. S.
Published: September 2007

In a study of triplets and higher multiple births in Western Nigeria, the incidence of triplets was found to be approximately 1–6 per 1000 maternities. The expected incidence calculated by Hellin's ‘law’ was higher than the observed incidence. The twinning and triplet rates in Western Nigeria were found to be approximately 4 and 16 (i.e. 42) times the corresponding rates in U.K. and U.S.A. Using data on sex the method described by Allen (1960) indicated that there was a relatively higher proportion of trizygotic triplets in the Nigerian population.
INBREEDING WITH SELECTION and LINKAGE
Authors: REEVE E. C. R.
Published: September 2007

General formulae are given for calculating the rate of progress towards fixation, and the equilibrium frequencies, at a locus (A, B) under selfing, when different selection intensities act against the two alternative homozygotes, and the selection intensities acting within and between lines are also different.

It is shown that selection between lines is much more powerful than selection within lines in slowing down progress or preventing fixation.

Formulae are given for calculating the rate of progress towards fixation of a pair of alleles (a, b) which are not directly affected by selection but are linked to the pair (A, B) subject to within line ami between line selection against homozygosis. The effects of different selection intensities are examined. Very strong selection, sufficient to keep most of the population heterozygous for A/B, leads to a loss of heterozygosity at the (a, b) locus of 2y(l–y) per generation, where y is the recombination frequency. With selection just preventing fixation at the {A, B) locus, the rate of loss of (a/6) heterozygotes is at first more rapid, but approaches asymptotically the rate of 2y(l–y). Selection acting only within lines has a much milder effect on the rate of progress at the (a, b) locus.

The effects on inbreeding progress of linkage of the {a, b) locus, not itself under selection, to one and to two pairs of lethals, are compared (Table 8). It appears that severe selection against homozygosis at a few points on a chromosome could reduce considerably the rate of progress towards fixation by inbreeding; and it is suggested that, as inbreeding progresses, the severity of this type of selection, and the number of loci at which it acts, will generally increase, so that the average progress towards fixation will fall more and more behind that expected on the classical theory, as the coefficient of inbreeding increases.
‘Secondary’ isozymes derived from the three PGM loci
Authors: FISHER R. A. , HARRIS HARRY
Published: September 2007

1. The isozymes derived from the human phosphoglucomutases ‐ PGM1, PGM2, PGM3 have been examined in three tissues (lymphocytoid cells, placentae and red blood cells) in which the average age of the constituent proteins may be expected to differ. The appearance of one or more more negatively charged isozymes would appear to be correlated with increasing overall protein age. It is suggested that these are ‘secondry’ isozymes formed in vivo from the least negatively chared form which presumed to be the primary post translational product of the particular gene.

2. Changes in the PGM3, isozyme pattern have been observed on storage of the placental extracts. Both the primary and the secondary in vivo isozymes were similarly affected. The storage effects observed are possibly due to reaction with red cell oxidized glutathione contaminating the extract. They may lead to confusion in typing unless controlled. Similar changes were not observed with the PGM1, and PGM2, isozymes.

3. The effects of a number of thiol reagents on the three PGMs have been examined and various changes in isozyme pattern have been produced artificially. Both the primary and the secondary in vivo isozymes derived from each allele were similarly affected by any particular treatment. PGM3, isozymes were more reactive with thiol reagents than PGM1, or PGM2, isozymes. These findings suggest that the primary and secondary isozymes derived from each of the three PGM loci each contain at least one reactive sulphydryl group. However, the in vivo changes by which secondary isozymes are generated do not appear to be due to such thiol effects.
Linkage studies on Peptidases A, B, C and D in man
Authors: COOK P. J. L. , POVEY SUSAN , ROBSON ELIZABETH B.
Published: September 2007

Linkage data obtained from studies on families segregating for electrophoretic variants of red cell peptidases A, b, C, D, are presented in the form of lod scores and of recombinants and non‐recombinants. No significant linkages were found, but ‘hints’ of linkage between pep B and Gm, between Pep C and Rh, and between Pep D, Lu and Secretor are discusse. There appears to be no close linkage between the four peptidase loci A, B, C, and D.
Metameric ‘Color Rule’ matches of normal, colour deficient, cataractic, and aphakic observers
Authors: KALMUS H.
Published: September 2007

Metameric matches on the ‘color rule’ under various kinds of illumination, principally of colour temperature 6500°K and 2400°k, were established for colour normal people of both sexes, various ages and ethnic origin. The matches shift in a way which is explicable by the yellow discoloration of the lens and possibly other optic media, with age and general pigmentation.

Individuals defective in colour perception differ ‐ as a group ‐ from normal people not only in the position of the average match co‐ordinates, but mostly also in a wider tolerance of accepted matches. By combining average match with tolerance area a useful criterion can be shown to exist for discriminating between normal, protanomalous and deuteranomalous people and to a lesser extent between the two principal classes of dichromats. Similar distinctions can be derived by inspecting the orientation and position of tolerance areas, which for red‐green defects are diagonally oriented but in one tritan defective appeared horizontal.

The versatility, cheapness and convenience of the ‘color rule’ for colour vision studies in the field is pointed out.
The amount of hereditary disease in human populations
Authors: TRIMBLE BENJAMIN K. , DOUGHTY JOHN H.
Published: September 2007

The frequencies of occurrence of various types of genetic disease have been derived for a number of successive annual birth cohorts from a well‐defined geographic region with a current population in excess of two million people. The results indicate that about 9·4 individuals out of every 100 liveborn will have serious genetic diseases or handicaps and that another 2·7 persons out of every 100 born alive suffer from disorders of unknown aetiology. However, the incidence of simple, dominant conditions is probably very close to 8 in every 10,000 liveborn, or about 12 times lower than previously believed. Accordingly, estimates of the risk to human health from these diseases, due to an artificially induced increase in mutation rate in man, may be some 12 times too high.
The genetics of the Lp Antigen
Authors: SING C. F. , SCHULTZ JANE S. , SHREFFLER D. C.
Published: September 2007

Several genetic models were considered to explain the distribution of qualitatively positive and negative children in 204 Caucasian families. A model which best describes the inheritance of the Lp antigenic expression involves a major genetic locus which distinguishes two overlapping continuously distributed modes of quantitative activity.
An interpretation of human diaphorase isozymes in terms of three gene loci DIA1, DIA2 and DIA3
Authors: FISHER R. A. , EDWARDS Y. H. , PUTT W. , POTTER J. , HOPKINSON D. A.
Published: September 2007

NADH and NADPH diaphorase isozymes have been studied in human tissues. Evidence from rare heterozygotes suggests that the red cell and main tissue forms of NADH diaphorase are products of the same locus DIA1 NADPH‐dependent diaphorase appears to be the product of a second locus DIA2 A third locus, DIA3 codes for the polymorphic sperm diaphorase. The products of this locus are also found in foetal tissues including placenta and adult brain and gonads. The products of these three loci may be distinguished by their substrate specificity, thermostability and molecular size.
The linkage relationships of the haemoglobin beta, delta and alpha loci with 34 genetic marker systems
Authors: WEITKAMP L. R. , STAMATOYANNOPOULOS G. , ROWLEY P. T. , KIRK R. L.
Published: September 2007

An analysis of the linkage relationships of the Hbα, and Hbβ, loci with 34 genetic marker systems is presented. No evidence of linkage of either haemoglobin locus with any of the marker loci was found. The Hbα, locus may be excluded from approximately 7% and the Hbβ, locus from approximately one‐third of the autosomal genome.
Tracing quantitative measurements on human chromosomes in family studies
Authors: LAUDER I. J.
Published: September 2007

Statistical methods are developed for tracing quantitative measurements on human chromosomes from parents to offspring. Tests for transmission are briefly considered.
Inverting the information matrix in gene‐frequency estimation in systems like ABO
Authors: LARSEN S. OLESEN
Published: September 2007

It is shown that the matrix of second‐order derivatives of the log likelihood function in the case of ABO‐like systems can be subjected to explicit inversion in the general case of k antigens.
Search of heterozygosis in quantitative characters
Authors: Smith Cedric A. B. , Loesch Danuta Z. , Bener Abdülabari
Published: September 2007

A method is described of searching for heterozygotes in a quantitative character, based on the idea that heterozygotes have more variable children than homozygotes. The variability in a set of sibs is therefore partitioned into components from the mother and father, using a least squares technique; a large component indicates a probably heterozygous parent. The method is tried out on dermatoglyphic data.
Down syndrome, paternal age, maternal age and birth order
Authors: ERICKSON J. DAVID
Published: September 2007

Recent cytogenetic evidence has shown that trisomy 21 can arise, perhaps even in substantial proportion, from paternal nondisjunction. The statistical association between Down syndrome incidence and maternal age, paternal age and birth order has been studied in a sample of over 4000 cases. The size of this sample made it possible to control for the effect of maternal age by single years of age during the search for a paternal age effect and vice versa, and the importance of such stringent control is emphasized.

The maternal age association was confirmed with an extremely high degree of statistical significance while no independent effect of paternal age was found; indeed, the rates at paternal ages over 45 years appear to be nearly constant. After adjusting for the effects of parental age, a significant inverse association of birth order with incidence was noted. It also appears that the incidence among very young mothers may be high: for maternal ages 15 years and less the rates seem to be equivalent to those found at 30 or 35 years. In order to help answer the question of whether the maternal age association is the result of increasing rates of nondisjunction or of some other mechanism (for example, an age related defect in a spontaneous abortion screening mechanism), the proportion of cases due to maternal and paternal nondisjunction at different parental ages must be determined.
The origin of human triploidy: an integration of qualitative and quantitative evidence
Authors: BEATTY R. A.
Published: September 2007

1. The origins of human triploidy are inferred from marker chromosomes by use of maximum‐ likelihood models applicable to all mammals with a simple XX: X Y sex determination mechanism. The numerical data comprise a compilation from the literature of 323 triploids and two 2N/3N mosaics, nearly all spontaneously aborted.

2. In the particular data, at the time of conception, it is estimated that digynic triploidy (two sets of maternal chromosomes) is less common than diandric (two paternal sets), and that dispermy (fertilization by two spermatozoa) exists and is commoner than diplospermy (fertilization by a diploid spermatozoon) as a cause of diandry: the best estimate of the diplospermic contribution is zero. A low viability of XYY conceptuses has been detected and measured, and is an essential factor in all interpretations: one consequence is that ˜ 15 % digynic triploidy at conception would change to ˜ 19 % at the time of scoring conceptuses. The viabilities of XXX and XXY are comparable with one another.

3. Inferences about the general population of triploids at conception are based on approximate confidence limits for the estimates. Digyny probably accounts for at most ˜ 41 % of all triploidy (perhaps as little as ˜ 7%). Diandric triploidy forms a major class (˜ 59‐˜ 93%) attributable at least in part to dispermy. The best estimate of diplospermic triploidy is zero, but it could account for up to ˜ 20 % of all triploids and up to ˜ 31 % of all diandric triploids. The low viability of XYY triploids remains marked as a population characteristic.

4. Certain items of indicative ‘ancillary evidence’ are used minimally, primarily as independent checks of the analytical results. They are: (a) that XYY have a low viability, (b) XXX and XXY have a comparable viability, (c) diplospermy plays little or no part in the genesis of triploidy, (d) some triploids are dispermic, (e) F‐body studies can estimate the relative numbers of XX, XY and YY diploid spermatozoa, (a), (b) and (d) are predicted correctly when (c) is used to guide analysis: (a), (c) and (d) when (b) and (e) are so used. This gives some confidence in the validity of the analyses, and in the reality of phenomena established from both qualitative and quantitative evidence.

5. The bulk of human triploidy probably arises near the time of fertilization.
The role of kin‐structured migration in genetic microdifferentiation
Authors: FIX ALAN G.
Published: September 2007

Most current models of human population structure view migration solely as a deterministic force reducing the variance in gene frequencies among the local colonies of a subdivided population. By an empirical example and through simulation experiments, it is shown that migration structured along kinship lines (by analogy to the lineal or ‘kinship’ effect) does not always reduce the variances of gene frequencies arising through intergenerational random genetic drift. Thus populations experiencing high rates of migration may not be genetically homogenous.
A cytogenetic study of 1000 spontaneous abortions
Authors: HASSOLD T. , CHEN N. , FUNKHOUSER J. , JOOSS T. , MANUEL B. , MATSUURA J. , MATSUYAMA A. , WILSON C. , Yamane J. A. , JACOBS P. A.
Published: September 2007

Cytogenetic analysis of 1000 spontaneous abortions showed 463 to have an abnormal chromosome constitution. The proportion of chromosome abnormalities varied with the gestational age of the abortus and the type of tissue cultured but was not significantly different among the five racial groups represented in the study population. It was suggested that differences in the rate of chromosome abnormalities among cytogenetic studies of spontaneous abortions were the result of methodological differences in sample selection rather than real biological variation among study populations. The only factor found to be unequivocally associated with the aetiology of chromosome abnormalities in spontaneous abortions was increasing maternal age in trisomies.
The position of the Radin blood group locus in relation to other chromosome 1 loci
Authors: LEWIS M. , KAITA H. , PHILIPPS S. , GIBLETT E. R. , ANDERSON J. E. , McALPINE P. J. , NICKEL B.
Published: September 2007

Data are presented which indicate that the Radin blood group antigen is governed by a locus, for the present called Rd, which is located between PGM1 and αFUC Rh, and is either very closely linked to or identical with Sc.
An empirical test of the two‐threshold model of disease transmission
Authors: PAULS D. , SINGER S.
Published: September 2007

Recent research on diabetes mellitus has revealed the existence of at least two independent subtypes. The multifactorial analysis method suggested by Reich & co‐workers (1972) for testing the independence of transmission between subtypes of a complex disorder agrees with this distinction. These techniques were also sensitive to the non‐unitary nature of the mental retardation within a sample of subjects drawn from the data set of Reed & Reed (1965). Therefore, we believe that this analysis could be a valuable adjunct to the limited repertoire of methods currently available to psychiatric researchers for dealing with issues of differential diagnosis.
The MNSs blood groups of families with chromosome 4 rearrangements
Authors: COOK P. J. L. , LINDENBAUM R. H. , SALONEN R. , CHAPELLE A. DB LA , DAKER M. G. , BUCKTON K. E. , NOADES J. E. , TIPPETT P.
Published: September 2007

SUMMAEY

Linkage analyses of the MNSs groups of families with chromosome 4 rearrangements support the assignment of the MNSs locus to chromosome 4 in the region q28‐q31.
The Gm‐Pi linkage heterogeneity in view of Pi M subtypes
Authors: JR T. GEDDE‐DAHL , FRANTS R. R. , OLAISEN B. , ERIKSSON A. W. , LOGHEM E. VAN , LAMM L.
Published: September 2007

In this study linkage between the loci for Gm (γ‐type heavy‐chain immunoglobulin markers) and Pi (α1‐antitrypsin/α1‐protease inhibitor) has been shown in families segregating for the Pi M subtypes (Ml, M2, M3 and Msal) as identified by separator isoelectric focusing. The estimate for the Gm‐Pi (M‐type) recombination is 0‐29 (95% limits 0‐24‐O37) at a peak lod score of 4‐31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm‐Pi in Pi MS (0‐26) and Pi MZ, SZ and FZ families (0 21). The overall Gm‐Pi recombination fraction estimate of 0 26 (95 % limits O23‐0‐30) at a peak lod score of 20‐75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M= 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the α1‐antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.
Juvenile insulin‐dependent diabetes: a possible susceptibility gene in interaction with HLA
Authors: CLERGET‐DARPOUX F. , BONAÏTI‐PELLIÉ C. , DESCHAMPS I. , HORS J‐ , FEINGOLD N.
Published: September 2007

A model with a susceptibility gene unlinked to HLA but in interaction with this system is shown to fit the data on familial distribution in 30 multiplex families of juvenile insulin‐dependent diabetes.
The biochemical genetics of human γ‐aminobutyric acid transaminase
Authors: JEREMIAH S. , POVEY S.
Published: September 2007

1. Two methods have been devised for the detection after electrophoresis of γ‐aminobutyric acid transaminase (GABAT) isozymes.

2. GABAT isozymes can be detected in liver, brain, kidney, pancreas, heart, testis, spinal cord and upper jejunum. The greatest activity occurs in liver.

3. Three different commonly occurring electrophoretic types of GABAT have been identified. It seems likely that they are determined by two alleles at an autosomal locus (GABAT).

4. The gene frequencies of GABAT1 and GABAT2 in a random sample of European livers were 0.56 and 0.44 respectively.

5. The three banded patterns seen in heterozygotes suggest that GABAT is a dimeric enzyme.

6. GABA, β‐alanine and 5‐aminovaleric acid can act as substrates for GABAT.

7. GABAT activity can be demonstrated in all areas of human brain with the exception of the corpus callosum. Brain samples from patients with Huntington's chorea show no abnormal GABAT activity or unusual phenotypes.
Deficiency of malic enzyme: a possible marker for malignancy in lymphoid cells
Authors: POVEY S. , JEREMIAH S. , ARTHUR E. , BER R. , FIALKOW P. J. , GARDINER E. , GOODFELLOW P. N. , KARANDE A. , KLEIN G. , QUINTERO M. , STEEL C. M. , ZEUTHEN J.
Published: September 2007

Soluble malic enzyme (MES) has been examined in long‐term human lymphoid cell lines cultured from 101 individuals. In 65 out of 66 lines derived from people without lymphoreticular malignancy the enzyme was very active. Lines established from 35 individuals with various forms of lymphoreticular malignancy were also examined, including in some cases more than 1 line derived from the same patient. In all cases where the cell line was thought to be derived from normal cells MES was active, but in 27 out of 29 lines thought to be derived from malignant cells (from 25 patients) MES was not detected. In the case of two patients with chronic lymphatic leukaemia ‘normal’ lines active for malic enzyme, and ‘leukaemic’ lines lacking malic enzyme, had been cultured from the same individual. Preliminary investigations of the lack of malic enzyme in somatic cell hybrids derived from lymphoma and leukaemia cell lines are compatible with an alteration at the level of the structural locus MES on chromosome 6. However, the restoration of MES activity in one line by fusion with mouse teratocarcinoma cells suggests that the alteration may be of a regulatory nature.
Multiple genetic relationships: joint and conditional genotype probabilities
Authors: Karigl G.
Published: September 2007

Li and Sacks derived joint and conditional genotype distributions for two relatives, neither of whom is inbred, by means of three basic stochastic matrices. These results have been generalized by Jacquard to handle consanguinity in the pedigree. It is the aim of this paper to extend the approach based on the concept of identity states to arbitrary multiple relationships. Joint and conditional genotype and phenotype probability distributions are derived for any number of individuals and applications to situations with up to three individuals are considered.
Glucose‐6‐phosphate dehydrogenase deficiency: genetic heterogeneity in Sardinia
Authors: FENU M. P. , FINAZZI G. , MANOUSSAKIS C. , PALOMBA V. , FIORELLI G.
Published: September 2007

Glucose‐6‐phosphate dehydrogenase (G6PD) was partially purified from red blood cells of 44 Sardinian males with severe enzymatic deficiency and the variants characterized chromatographically and biochemically to see if there is genetic heterogeneity of the enzyme in Southern Sardinia. Three different variants associated with severe G6PD deficiency were identified: the common G6PD Mediterranean variant; G6PD Sassari, recently described by Testa et al. (1980), and a new variant that we have designated G6PD Cagliari. Family studies were carried out to demonstrate that these variants are due to the presence of different alleles.
Chiasma derived genetic maps and recombination fractions: chromosome 1
Authors: HULTÉN M. A. , PALMER R. W. , LAURIE D. A.
Published: September 2007

Chiasma distribution data from six human males have been used to calculate genetic distance and recombination fraction for chromosome 1. Estimates given for each major chromosome band are valid only under the assumption that there is no chromatid interference, no chiasma movement, and no differential chromosome contraction between mitosis and meiosis.
Molecular studies of liver aldolase B in hereditary fructose intolerance using blotting and immunological techniques
Authors: GRÉGORI C. , SCHAPIRA F. , KAHN A. , DELPECH M. , DREYFUS J.‐C.
Published: September 2007

Hereditary fructose intolerance is due to a deficiency of liver aldolase (aldolase B). Little is known about its molecular mechanisms. We have tried to demonstrate the presence of the molecule and have explored the possibility of genetic heterogeneity.

Investigations included:

Liver samples from fifteen cases of hereditary fructose intolerance due to aldolase B deficiency were studied by various electrophoretic techniques. After electrophoresis on polyacrylamide gels, proteins were electrophoretically transferred on to nitrocellulose filters. They were treated with specific antialdolase B antibodies, and then with radioiodinated protein A, followed by autoradiography.

(a) sodium dodecyl sulphate electrophoresis, in order to detect the presence of immunologically

(b) attempts to discover charge anomalies of the native molecule and of its subunits, by the

Isoelectric focusing of the native enzyme.

Isoelectric focusing and non‐equilibrium pH gradient electrophoresis (NEPHGE) after

The major results were the following:

(1) In all cases a cross‐reacting material was found, with a molecular subunit size of 38000,

indistinguishablc from that of controls.

(2) Evidence for molecular heterogeneity of the disease was provided by two types of data: amount of apparent immunologically reactive protein, which varied from less than 3 % to 100 % of that of controls; and charge data, aldolase B from seven patients showing an increased negative charge and from one patient a normal charge.
Genetic linkage data for the Dombrock blood group locus relative to chromosome 1 and chromosome 4 loci
Authors: LEWIS M. , KAITA H. , PHILIPPS S. , GIBLETT E. R. , ANDERSON J. E.
Published: September 2007

Odds favouring Do: PGD linkage (ž+ 3.56 at θ= 0.23) based on the average antilod are 920:20≃46:1. If Do is located on chromosome 1 it lies distal to PGD and recombination between PGD and Do occurs more frequently in male than in female meioses. Our data do not support Do:GC linkage.
Absence of close linkage between Hereditary Spherocytosis (SPH) and 24 genetic marker systems including HLA and GM
Authors: JONGH B. M. de , BLACKLOCK H. A. , REEKERS P. , VOLKERS W. S. , KHAN P. MEERA , BERNINI L. F. , NIJENHUIS L. E. , van LOGHEM E. , SCHREUDER G. M. Th. , ROOD J. J. van
Published: September 2007

A total of 250 individuals belonging to 19 different families, identified through established propositi were simultaneously screened for hereditary spherocytosis (SPH), using stringent criteria, and 27 well‐known polymorphic genetic marker systems.

The segregation analysis indicated that the pattern of inheritance of SPH in these families, being autosomal and dominant, had a 100 % penetrance. A statistical analysis, using the LIPED computer program of Ott (1974), revealed the absence of close linkage between SPH and AB0, ACP1, ADA, AK1, C3, D1A2, ESD, FY, CC, GL01, GM, GPT1, HLA, HPA, JK, K, KM, MNS, P, PGD, PGM1, PGP, PI, and RH.

Since an earlier study by other investigators had convincingly suggested a linkage between SPH and GM, we subjected the data to further analysis and found no significant heterogeneity in our recombination values of linkage between SPH and GM, or any of the other informative loci.
Relative importance of genetic and nongenetic etiologies in idiopathic mental retardation: estimates based on analysis of medical histories
Authors: COSTEFF H. , COHEN B. E. , WELLER L.
Published: September 2007

A method of analyzing subgroups of mental retardates for proportions of cases caused by nongenetic brain damage is presented here and applied to 490 Israeli retardates.

Among mild retardates in simplex and multiplex families with normal unrelated parents, most of the cases were caused by nongenetic brain damage and only a minority were caused by polygenic heredity. Among severe retardates in multiplex families with normal unrelated parents, nongenetic brain damage is probably a more important cause than is homozygosity. In all groups except two (mild retardates with normal consanguineous parents, and severe retardates with retarded parents) the contribution of nongenetic brain damage was surprisingly large.
Effect of population associations and reduced penetrance on observed and expected genotype frequencies in a simple genetic model: application to HLA and insulin dependent diabetes mellitus
Authors: FALK C. T. , MENDELL N. R. , RUBINSTEIN P.
Published: September 2007

The observed and Hardy‐Weinberg‐expected frequencies for (HLA) marker heterozygotes in a disease population are calculated where it is assumed that the disease is caused by either homozygosity or heterozygosity (with reduced pentrance) for a disease susceptibility allele at a disease locus, that allele being positively associated with both of the relevant alleles at the marker locus (the single susceptibility allele model of Svejgaard & Ryder, 1981). It is shown that the observed frequency is always less than or equal to the H‐W expectation, with the (observed/expected) ratio decreasing as the degree of dominance increases.
Triple chromosome synapsis in oocytes from a human foetus with trisomy 21
Authors: WALLACE B. M. N. , HULTÉN M. A.
Published: September 2007

Oocytes from a human foetus with trisomy 21 were spread using detergent and examined by light and electron microscopy. The three chromosomes 21 occurred as bivalent and univalent or trivalent configurations. In the trivalents the lateral elements of the synaptonemal complex were associated in threes, either completely along the length of the trivalent, or partially, forming a variety of forked structures. This triple association demonstrates that, contrary to the classical view of chromosome pairing, three homologous chromosomes can be held in register at the same site.
Chiasma‐derived genetic lengths and recombination fractions: a reciprocal translocation 46, XY, t(1; 22) (q32; q13)
Authors: PALMER R. W. , HULTÉN M. A.
Published: September 2007

The chiasma distribution in a human male carrier of a balanced reciprocal translocation 46, XY, t(1; 22) (q32; q13) has been compared with data from six controls. The translocation carrier shows a raised chiasma frequency and altered chiasma distribution in chromosome 1, particularly in the region adjacent to the breakpoint. These changes are expected to distort the recombination pattern, implying that caution should be taken when trying to incorporate linkage data from translocation families into the normal genetic map.
The human glutathione S‐transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes
Authors: Strange R. C. , Faulder C. G. , Davis B. A. , Hume R. , Brown J. A. H. , Cotton W. , Hopkinson D. A.
Published: September 2007

1. Three sets of isozymes of glutathione‐S‐transferase (GST) have been identified in human tissues. They differ in their tissue distribution, incidence of genetic variation, susceptibility to inactivation by N‐ethylmaleimide and in their electrophoretic mobilities.

2. The GST1 isozymes exhibit four phenotypes, including a common ‘null’ phenotype attributable to different combinations of three autosomal alleles GST1*1, GST1 *2 and GST1*0 of frequency 0·13, 0·23 and 0·64, respectively, in the European population.

The genetic polymorphism of GST1 is easily demonstrable in adult liver, kidney, adrenal and stomach but the isozymes are only weakly expressed in skeletal and cardiac muscle and not at all in fetal liver, fibroblasts, erythrocytes, lymphocytes and platelets.

3. The GST2 isozymes also exhibit variant patterns but these are probably due to post‐synthetic modification rather than allelic variation. The GST2 isozymes are not detectable in erythrocytes, platelets, cultured fibroblasts or lymphocytoid cells but are found in many other tissues, including fetal liver.

4. GST3 isozymes were found as relatively strong components in every tissue examined except adult liver, with slight tissue to tissue variability in electrophoretic mobility.
The marker (X) syndrome: a cytogenetic and genetic analysis
Authors: Sherman S. L. , Morton N. E. , Jacobs P. A. , Turner G.
Published: September 2007

The results of a cytogenetic and segregation analysis of 110 pedigrees of the mar (X) syndrome are reported. The cytogenetic study indicated an inverse relationship between IQ and the mar(X) frequency in females but not in males. A small but significant effect of age on mar(X) frequency was observed in both males and females, but in females it was restricted to those of normal intelligence, retarded females showing no significant effect.

Classical segregation analysis was performed using the program segran, analyzing sexes separately. a 20% deficit of affected males was observed, the most plausible explanation for the majority of these cases being incomplete penetrance. since this was an unexpected result, the data were scrutinized for possible biases; however, correction of these had little effect on the estimate. the penetrance of mental impairment in carrier females was estimated to be 30% and of mental impairment and/or mar(x) expression to be 56%. thus 44% of carriers cannot be detected with our definition of affection. no evidence for sporadic cases among affected males was found. complex segregation analysis was performed using the sex‐linked version of pointer analysing sexes together. this was done in order to test the results from classical segregation analysis, to test for family resemblance and to estimate mutation rates. it was confirmed that there was a 20% deficit of affected males, that, penetrance of mental impairment in females was approximately 30% and that there was no evidence: for sporadic: males. thus all males with the gene appear t o have received it from their carrier mothers and all mutations must occur in sperm. the mutation rate in sperm was estimated to be as high as 7·2 × 10‐4, implying that over one‐half of random carrier females are fresh mutants.

our results have important implications for genetic counseling as they imply that all mothers of isolated affected males are carriers, that normal brothers of affected males have a 17% chance of carrying the gene and transmitting it to all their daughters, and that normal sisters of affected males have, at most, a 30% chance of being carriers. since there are biases in the data due to the testing of particular individuals, these probabilities must be considered approximations until they are independently confirmed.
Assignment of the human gene for peptidase E to the chromosomal region 17q23 → 17qter
Authors: Wilson D. , Harrison B. , Caron P.
Published: September 2007

Peptidase E has been studied in 16 independent human‐Syrian hamster hybrids and 16 subclones. Evidence is presented indicating that the human gene for Peptidase E is on chromosome 17 in the region 17q23 → 17qter.
Confirmation of the regional localization of the genes for human acid alpha‐glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization
Authors: Honig J. , Martiniuk F. , D'Eustachio P. , Zamfirescu C. , Desnick R. , Hirschhorn K. , Hirschhorn L. R. , Hirschhorn R.
Published: September 2007

We have confirmed the localization of human acid alpha‐glucosidase (GAA) to 17q21 → q25 and of adenosine deaminase (ADA) to 20q13 → 20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter → 17q25:: 20q13 → 20qter; 20pter → 20q13:: 17g25 → 17gter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21 → 22) or the 17/20 (17pter → 17q25:: 20q13 → 20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha‐glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25 ‐0 17qter reported by Nickel et al. (1982). Combined with earlier results (Weil et al. 1979), GAA can be assigned to 17q21 → 17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2 → qter by gene dosage studies (Philip et al. 1980).
Calculation of recurrence risk in the case of ankylosing spondylitis taking into consideration the antigen HLA‐B‐27
Authors: Gömör B. , Ratkó I.
Published: September 2007

The authors have provided a new recurrence risk table of ankylosing spondylitis. The mathematical problem solved was to combine a continuous distribution for polygenic inheritance with a discrete one, HLA‐B‐27 antigen ‘yes’ or ‘no’. Previously the highest probability of recurrence was 0.0785 in the case of an affected mother's son and it increased to 0.1416 when the B‐27 antigen positive affected mother had a B‐27 positive son.
Fetal death rates in mothers of children with trisomy 21 (Down syndrome)
Authors: Lippman A. , Aymé S.
Published: September 2007

Women under 25 years at the birth of a child with trisomy 21 (Down syndrome) appear to have an increased risk of having another child with a trisomy. If the risk of recurrence is due solely to an increased production of trisomic conceptions, women with an affected child should have a rate of spontaneous abortion higher than average, since the majority of aneuploid conceptuses are expected to be aborted. We examined fetal loss rates among the other pregnancies of 545 women delivered of a child with trisomy 21 and compared the observed loss rates with those which would be expected were the relative risk for these women for an aneuploid recognized pregnancy the same as their relative risk for an aneuploid livebirth as reported by others. Overall loss rates in their prior pregnancies were greatest for women who were 20–24 years old at the time of birth of the proband. Moreover, the observed rate of fetal loss for this group of women (33·8%) was at least as high as that predicted from their relative risk for a trisomic livebirth. By contrast, the observed fetal loss rates for women 25–39 years of age at the proband's birth did not differ from the rates predicted on the assumption that their risk for a trisomic recognized pregnancy was not increased, as the livebirth data suggested. The results of this study suggest that women under 25 years at the birth of a child with trisomy 21 have a significantly higher rate of fetal loss in their prior pregnancies than women delivered of the trisomic child at older ages.
A computer program for constructing a maximum‐likelihood map from linkage data and its application to human chromosome 1
Authors: Wedd N.
Published: September 2007

An algorithm is described which attempts to find the maximum likelihood order of the loci on a chromosome using linkage data. It can also use data on locus order if these are available. A computer program which applies this algorithm has been written, and tested on the data for human chromosome 1. The most likely possible order is GDH, PGD, ENO1, Rh, UMPK, Sc, PGM1, AMY, Fy, CAE, 1qh, CMT1, AT3, PEPC.
Parental origin of autosomal trisomies
Authors: HASSOLD T. , CHIU D. , YAMANE J. A.
Published: September 2007

Chromosome heteromorphisms of parents and their trisomic spontaneous abortions were compared in an attempt to determine the parental origin of 204 single trisomies, including cases of trisomy 3, 4, 9, 13, 14, 15, 16, 21 and 22, nine mosaic trisomies and nine double trisomies. Non‐disjunction at maternal meiosis I was the most likely source of the additional chromosome for all trisomies studied, including the mosaics, and this was the case at all maternal ages. However, trisomy 21 had a significantly increased proportion of paternally derived cases by comparison with all other trisomies. Consideration of the sex ratio in eases of trisomy 21 of known parental origin suggests that there is an excess of males associated with paternal first meiotic division non‐disjunction. The fact that this mechanism of origin is more prevalent in trisomy 21 may well explain why there is an excess of males associated with this abnormality but not with other autosomal trisomies.
Human myosin heavy chain genes assigned to chromosome 17 using a human cDNA clone as probe
Authors: EDWARDS Y. H. , PARKAR M. , POVEY S. , WEST L. F. , PARRINGTON J. M. , SOLOMON E.
Published: September 2007

A cDNA clone complementary to the mRNA encoding human myosin heavy chain has been isolated from a human fetal skeletal muscle cDNA library. A 600 base pair fragment of the inserted human cDNA has been used as probe in the Southern analysis of DNA from panels of rat/human and mouse/human somatic cell hybrids. All the sequences detected by this probe have been mapped to chromosome 17 in the region 17pter → 17p11. There was no evidence for MHC sequences on any other chromosome.
Heritable fragile sites on human chromosomes XII. Population Cytogenetics
Authors: SUTHERLAND G. R.
Published: September 2007

Chromosome studies to detect the folate sensitive fragile sites have been carried out on 2439 randomly selected neonates. Four autosomal fragile sites were detected in this group. Similar studies were carried out on referred patients, special school students and sheltered workshop employees. The incidence of fragile X in these groups was 6/1936, 13/502 and 0/128 respectively. Autosomal folate sensitive fragile sites were seen in 14/1936, 5/502 and 2/128 individuals respectively.
The structural gene for aldolase B (ALDB) maps to 9q13→32
Authors: HENRY I. , GALLANO P. , BESMOND C. , WEIL D. , MATTEI M. G. , TURLEAU C. , BOUÉ J. , KAHN A. , JUNIEN C.
Published: September 2007

We used a cloned cDNA probe for the B subunit of human aldolase (ALDB) and Southern blotting techniques to analyse DNA from a series of rodent x human somatic cell hybrids for the presence of specific ALDB‐related sequences. Our results provide evidence for the assignment of the gene for ALDB to chromosome 9. Moreover, by direct gene dosage determination in two patients with chromosome 9 unbalanced rearrangements and by in situ hybridization we refined the regional chromosomal assignment to 9q13→q32 and most probably to 9q21.3→9q22.2.
Further studies on chiasma distribution and interference in the human male
Authors: LAURIE D. A. , HULTÉN M. A.
Published: September 2007

Some unusual patterns of chiasma distribution were noted in a preliminary investigation of meiosis in an infertile male with an apparently normal mitotic karyotype and a normal mean autosomal cell chiasma frequency. A detailed investigation of chiasma distribution on all 22 autosomes revealed that several chromosomes showed a significant change in chiasma distribution and/or mean inter‐chiasma distance in comparison with previously published controls. These findings are discussed in relation to the general patterns of chiasma localization in the human male and the role of interference.
Possible changes in the frequency of the human ABO blood groups in Iceland due to smallpox epidemics selection
Authors: ADALSTEINSSON S.
Published: September 2007

The hypothesis is put forward that the low frequency of A and high frequency of O blood group genes in the Icelandic human population is the result of a selective disadvantage of A during severe smallpox epidemics. The hypothesis is supported by data from India in 1965–6, which show a marked selective effect of a smallpox epidemic against the phenotypes A and AB (Vogel & Chakravartti, 1971). The conclusion is drawn that the present‐day ABO blood group gene frequencies of the Icelandic population should be used with reservation as markers in the study of the origin of the Icelanders.