bluuebunny/crossref_metadata_2025 huggingface dataset:
A statistical and genetical study of diabetes I. Prevalence and morbidity
Authors: FALCONER D. S. , DUNCAN L. J. P. , SMITH CHARLES
Published: September 2007

1. Records of current age and onset age of known diabetics resident in Edinburgh and alive at 1 January 1968 were obtained. Ascertainment was estimated to be between 90 and 95% complete.

2. The overall prevalence was 0–57% in males and 0–67% in females.

3. The age‐specific morbidity risks were estimated by a new method which uses the information from all living diabetics by relating the frequency to the duration of the disease.

4. The morbidity risk increases continuously with age and reaches 2 % per annum at the age of 70, after which it levels off but does not decline.

5. Cumulation of the annual morbidity risks leads to estimates of the ‘potential prevalence’ at successive ages. This is the prevalence expected if the mortality of diabetics was the same as that of the non‐diabetics and if the morbidity risks were the same as they are now. The potential prevalence increases with age faster than the actual prevalence; at 40 it is about twice as great and at 80 about eight times.

6. The difference between the actual and the potential prevalence may be due to higher mortality of diabetics or to the morbidity risk increasing with time, or to both. By analysis of the frequency of diabetics in relation to the duration of the disease and the date of diagnosis estimates were made of the rate of mortality or of the rate of increase of the morbidity risk.

7. Assuming constant morbidity risk, the additional annual mortality risk to diabetics is 1–2% at age 10, rising to 20% at age 80. Relative to the population, the mortality is 20 times at age 20 and 2 times at age 80.

8. Assuming no additional mortality, the morbidity risk would have to have increased by 1–2% per annum at age 10 and 8–10% per annum at age 60 to account for the difference between the actual and the potential prevalence. The number of registrations at the Clinic showed an increase of only 3 % per annum in males and no increase in females.
A distinctive pigment of the skin in New Guinea indigenes
Authors: WALSH R. J.
Published: September 2007

An unusual pigmentation of skin is described amongst indigenes of widely scattered areas in New Guinea. It is suggested that it is due to the accumulation of a red intermediary metabolite in the formation of melanin, and that it results from a metabolic error determined by an autosomal recessive gene. Pedigrees of thirty‐three families with red skins are presented and analysed. The pigment could not be identified by histochemical studies of biopsy specimens and a portable reflectance spectrophotometer did not define its characteristics. The gene is present in high frequency in some areas in which it must possess a significant survival advantage.
Placentation and zygosity ot triplets and higher multiple births in Ibadan, Nigeria
Authors: NYLANDER P. P. S. , CORNEY G.
Published: September 2007

Placentation and zygosity were studied in forty‐four sets of triplets and 1 set of quadruplets in Ibadan, Western Nigeria, between January 1967 and December 1969. Amongst those triplet sets with known placentation, 1 (2–5%) was monochorionic, 10 (25‐0%) were dichorionic and 29 (72‐5%) were trichorionic.

Zygosity was determined by sex, type of placentation and genetically determined characters in red cells and placental tissue. It was possible to determine the zygosity of forty sets of triplets and of these 2 (5‐0%) were likely to be MZ, 14 (35‐0%) were likely to be DZ and 24 (60‐0%) were TZ. The high proportion of TZ sets is consistent with previous reports of a high rate of DZ twinning in the same population as compared with other Negro and Caucasian populations.
Studies on the separate isozymes of red cell acid phosphatase phenotypes A and B
Authors: FISHER R. A. , HARRIS HARRY
Published: September 2007

Comparisons were made of some of the properties of the isozymes of types A and B red cell acid phosphatase. In each case, the more anodal isozyme had a higher pH optimum and a lower Km for ^‐nitrophenyl phosphate. Thermostability tests indicated that this isozyme was also the least stable in both types. Evidence is also presented which suggests that the two isozymes within one type are interconvertible.
Further studies on the molecular size of red cell acid phosphatase
Authors: FISHER R. A. , HARRIS HARRY
Published: September 2007

Estimates of the molecular weight of red cell acid phosphatase have been made by gel filtration under denaturing conditions, i.e. in 6 M guanidine hydrochloride. The results suggest a figure of 14,800 which is almost twice as high as previous estimates obtained by gel filtration in the native form.
Extension of the Hardy‐Weinberg Law to assortative mating
Authors: PRICE GEORGE R.
Published: September 2007

A relation is given between the degree of assortative mating in parents, which is measured by a weighted covariance, and the degree of departure from Hardy‐Weinberg conditions in offspring.
THE INHERITANCE OF MUSCULAR DYSTROPHY: FURTHER OBSERVATIONS
Authors: WALTON JOHN N.
Published: September 2007

The results are reported of a survey of the mode of inheritance of muscular dystrophy as determined from a series of sixty‐seven cases occurring in seventeen families.

In seven families containing cases of the Duchenne‐type muscular dystrophy there were thirty‐seven oases of which one appears to be female, although her polymorphonuclear leucocytes do not show female characteristics. Nevertheless in all families the mode of inheritance was characteristic of that due to a sex‐linked recessive gene. In three of the families the onset of the disease was as late as the second or third decade.

In three families of facioscapulohumeral dystrophy there were at least eleven affected individuals including three abortive cases. The pattern of inheritance suggested that this disease is carried as an autosomal dominant character, though possibly with sex limitation (to females) or incomplete manifestation in some families.

Nineteen cases of limb‐girdle dystrophy occurred in eight sibships of seven families; this form of the disease appears to be transmitted as an autosomal recessive character.

I am grateful to Dr E. A. Carmichael for his encouragement and advice during the course of this study and to the physicians and Medical Committee of the National Hospital, Queen Square, for permission to review these cases. I also appreciate the advice of Prof. L. S. Penrose and Dr Ursula Philip and the help given by Dr W. M. Davidson of King's College Hospital, London, Dr Ursula Mittwoch of the Galton Laboratory, and Dr R. B. Thompson of Newcastle upon Tyne in sexing the nuclei of case IV. 1 of family D. 1. I also acknowledge with thanks financial assistance given by the Muscular Dystrophy Associations of America, Inc. and the invaluable help of my secretary, Mrs B. Wilson.
X‐CHROMOSOMAL OCULAR ALBINISM IN A DUTCH FAMILY*
Authors: WAARDENBURG P. J. , VAN DEN BOSCH J.
Published: September 2007

A large Dutch family stock with X‐chromosomal ocular albinism is recorded. The first generations have been formerly described by Engelhard as cases of hereditary nystagmus. This nystagmus was present indeed in all the males and in the only female person affected, but it proved to be a secondary one. The patients showed a kind of albinoidism of the tapetum, which was not quite devoid of pigment. It was combined with a hypoplasia of the fovea as in generalized albinism. The question is discussed whether this type of albinism is fully restricted to the eye or not. The mode of inheritance is an intermediate one. The female carriers are recognizable as heterozygotes by diascleral translucency of their irides and by irregular peripheral pigmentation of their fundi. The method of examination employed by the authors is described. Stress is laid upon the practical value of this research because it is now possible for daughters of transmitter females to obtain a scientifically justified prognosis for their eventual offspring.
THE RELATIONSHIP BETWEEN PARENTAL AGE, BIRTH ORDER and THE SECONDARY SEX RATIO IN HUMANS*
Authors: NOVITSKI E. , SANDLER L.
Published: September 2007

An analysis is made of the change in secondary sex ratio in humans as the ages of the parents increase, and also as the age of the mother and birth order increases. It is shown that both age of the father and birth order are significantly correlated with this change in sex ratio, whereas the age of the mother is not. The changes with increasing birth order and with increasing age of the father are so similar when properly compared, that they appear quite likely to be caused by the same underlying factor.
NAIL‐PATELLA SYNDROME: EVIDENCE FOR MODIFICATION BY ALLELES AT THE MAIN LOCUS
Authors: RENWICK J. H.
Published: September 2007

Parent‐child correlations of approximately zero and sib‐sib correlations of approximately one‐half have beefi obtained in respect of the grade of seventy in the nail‐patella syndrome. The nail defect and the patellar size have been used as indices of severity.

These findings are interpreted as evidence for the operation of a series of modifying genes at the nail‐patella locus itself and a possible method of confirming this interpretation is suggested in which use is made of the known linkage between this locus and the ABO locus.
Isochromosome for the short arm of X, a human 46, XXpi syndrome
Authors: CHAPELLE ALBERT de la , SCHRÖUDER JIM , PERNU MAURI
Published: September 2007

Cytogeetical and clinical findings in a 17 year‐old female with te karyotype 46, XXpi are presented. The patient was 159 cm tall and had never menstruated. The gonads were not palpable and secondary sex characteristics were poorly developed. She had no somatic sgns of Turner's syndrome apart from a renal anomaly. The abnormal X chromosome could be identified as an Xpi by its characteristic fluorescence patterns and Giemsa staining properties after the ASG procedure. Autoradiography showed it to be the latest‐labelling chromosome in nearly all cells. Sex chromatin bodies were normal in number and decreased in size (79% of normal). These findings, taken with the incomplete data from two presumptive XXpi cases reported by others, indicate that the karotype 46, XXpi produces a clinical picture distinguishable from Turner's syndrome.

The proposita and her father were Xg(a+), and her mother Xg(a−), indicating paternal derivation of the normal X chromosome. Hence the Xpi appears to be of maternal origin. Other interpretations are possible.

The findings lend added support to the hupothesis that genes controlling gonodal development are carried in both Xp and Xq, whereas those affecting stature are in Xp but probably not in Xq.

It is proposed that at isochromosome formation Xqi is far more likely to be produced than Xpi. This may be because breakage preferentially occcurs at the short‐arm end of the centromere region or in the short arm itself, as indicated by the existence of presumptive dicentric Xqi chromosomes.
Distribution of gene frequencies in a geographically structured population III. Distribution of deleterious genes and genetic correlation between different localities*
Authors: MARUYAMA TAKEO
Published: September 2007

Distribution of gene frequencies and gentic correlation of different localities in a geographically structured population were investigated for various deleterious genes. Approximation formulae were obtained and they were checked by computer simulations. Effect of selection on the genetic correlation was discussed.
Probable assignment of the locus determining human red cell acid phosphatase ACP1 to chromosome 2 using somatic cell hybrids
Authors: POVEY SUSAN , SWALLOW DALLAS M. , BOBROW MARTIN , CRAIG IAN , HEYNINGEN VERONICA van
Published: September 2007

Twelve independent interspecific hybrid lines, from six different crosses, together with nine subclones, were tested for the presence of the human enzymes ACP1, MOR‐S and ICD‐S. The hybrids were also tested for a total of 27 other human enzymes. With one exception the data were consistent with the synteny of ACP1, MOR‐S and ICD‐S. Detailed chromosome analysis of the subclones confirmed the assignment of these loci to chromosome 2. In the remaining hybrid chromosome 2 was present, together with MOR‐S and ICD‐S but ACP1 was not seen. Possible explanations for this discrepancy are discussed.
A study of possible factors influencing the variation in liver alcohol dehydrogenase activity in individuals of the ‘usual’ ADH phenotype
Authors: AZEVÊDO ELIANE , SMITH MOYRA , HOPKINSON D. A. , HARRIS HARRY
Published: September 2007

The influence of five factors (cause of death, age at death, sex, ADH3 phenotype and time between death and autopsy) on the total levels of alcohol dehydrogenase (ADH) activity exhibited by crude extracts of human post‐mortem liver specimens in a series of 954 adult individuals have been examined.

The cause of death was found to be the most important factor: livers from patients dying from a sudden traumatic accident or illness of acute onset showed, on average, two or three times more ADH activity than the livers from patients dying of a chronic illness or cancer.

Age at death and sex appeared to have only small effects on total liver ADH activity: in general, samples from young adults showed slightly higher levels than samples from old people and males gave slightly more activity than females.

Liver ADH activity was not markedly influenced by ADH3 phenotype.

Delays of up to 10 days between death and autopsy seemed to exert little influence on the ADH activity of post‐mortem liver specimens.
Regulation in man × man somatic cell hybrids: possible negative control of Arylsulphatase A
Authors: HORS‐CAYLA M. C. , HEUERTZ S. , PICARD J. Y. , FRÉZAL J.
Published: September 2007

Quantitative assays demonstrate that the level of the lysosomal enzyme arylsulphatase A (ASA) is very low in the heteroploid human line D98 AH2.

Intraspecific cell fusion between that strain and human diploid fibroblastic strains has been obtained. Hybrid cells are distinguished by their karyotypes and by the electrophoresis pattern for phosphoglucomutase, locus PGM1.

ASA activity of hybrid cells was nearly as low as activity of the D98 AH2 line: deficiency is dominant over non deficiency.

Several hypotheses are discussed: one of them involves a negative control of the enzyme arylsulphatase A.
Early fusion of two human embryos?
Authors: CHAPELLE ALBERT DE LA , SCHRÖDER JIM , RANTANEN PENTTI , THOMASSON BJÖRN , NIEMI MIKKO , TIILIKAINEN ANJA , SANGER RUTH , ROBSON ELIZABETH B.
Published: September 2007

An infant chimaera with an XX and an XY cell line is described. She had a macroscopically and histologically normal ovary on the right and an ovotestis on the left. Biopsies from the gonads revealed 1–15% of XY cells as judged by fluorescent Y body findings of uncultured cells as well as by karyotypes of mitoses from long term cultures. Ovarian and testicular structures had similar frequencies of the two cell lines. There was no evidence of in vitro selection of cells during tissue culture.

In addition to the sex chromosomal evidence, two paternal contributions could be deduced from the segregation pattern in the proposita and her parents of the following systems: a fluorescent marker on chromosome 22, HL‐A antigens, Xgaand MNSs. Evidence for two maternal contributions came from a fluorescent marker on chromosome 3, HL‐A and ADA. The distribution of the two cell lines in different tissues was unequal, the frequency of the XY cells being 1–15% in gonadal tissues and approximately 90% in lymphocytes and erythrocytes.

The inheritance of the maternally derived fluorescent marker on chromosome 3 indicates that the two maternal nuclei cannot have been the ovum and the second polar body provided no crossing‐over had occurred between the centromere and band 3q11. Participation of one or both of the products of the first meiotic division (i.e. secondary oocyte nuclei) was discussed but thought to be improbable. It is therefore likely, but not formally proven, that the chimaera had originated from the early fusion of two separate embryos.
Enolase: human tissue distribution and evidence for three different loci*
Authors: CHEN SHI‐HAN , GIBLETT ELOISE R.
Published: September 2007

Four different cellogel electrophoretic patterns of enolase were found in human tissue extracts. They consisted cf:

one strongly stained band (I) and two minor bands (II and III) found in haemolysates, white cell, skin fibroblast and kidney extracts;

a three‐banded pattern in brain resembling that of haemolysates except for heavier concentrations of bands II and III;

a single component corresponding to band I, found in liver, heart, intestine, spleen and placenta;

a single band with slightly faster mobility than band I, found in adult muscle extracts.

The haemolysate of an individual with the heterozygous ENO11/ENO21, genotype had a triple‐banded pattern replacing band I, a double‐banded pattern replacing band IP and a single weakly staining band III. This finding, as well as the results of dissociation and recombination experiments, supports the hypothesis that the enzyme is a dimer formed by random interaction of two polypeptide chains (α and β) synthesized by two independent gene loci (ENO1, and ENO2,). Evidence for a third locus, ENO3, is supplied by the electrophoretic pattern of muscle extracts.
Ages of death of children with Huntington's Chorea and of their affected parents
Authors: VLIS M. VEGTER‐VAN DER , VOLKERS W. S. , WENT L. N.
Published: September 2007

Bird et al. (1974) noted an interesting ‘anticipation’ phenomenon in Huntington's Chorea occurring in patients who inherited the gene from their father. More extensive samples from 165 pedigrees in the Low Countries permitted us to show that most of this apparent ‘anticipation’ is an artifact due to sampling biases related to the year of birth categories of the affected parents. When these biases were excluded no differences exist between the ages of death of affected mothers and their affected children, but a small difference of approximately two ymrs remains between affected fathers and their affected children. This is explainable by the observation that juvenile cases of Huntington's Chorea usually have inherited the abnormality from their father.
Genetic markers in trisomies 13 and 18
Authors: CÔCTÉ GILBERT B. , EDWARDS J. H.
Published: September 2007

Data on centromeric linkage for trisomies 13 and 18 are presented. There is no substantial evidence that any of these loci studied are on either chromosome. There is weak evidence relating the locus defining the Kidd groups to chromosome 18.
Population structure of Barra (Outer Hebrides)
Authors: MORTON N. E. , SMITH C. , HILL R. , FRACKIEWICZ A. , LAW P. , YEE S.
Published: September 2007

Historical demography, surname concordance (isonymy), migration, and genealogy give a consistent description of population structure. The census size has averaged about 1400 over the last five centuries. Conjoined with an effective migration rate of 0.05 per generation as estimated by three different methods, this gives an evolutionary size of 638, random kinship of 0–008 and inbreeding of 0.007 relative to the rest of Britain. The population structure of Barra is similar to other British isolates in the recent past, but an order of magnitude less inbred than slash‐and‐burn agriculturalists and Pacific Islanders. Some consequences for rare genes and polymorphisms are discussed.
Test of the neutrality hypothesis
Authors: PRICE GEORGE R.
Published: September 2007

*Note. Dr Price died unexpectedly in January 1976 while he was working on the Kimura neutral gene hypothesis. He had been investigating methods of programming and using a significance teat, due to W. J. Ewens (1972), and had been applying them to the date on enzyme polymorphisms collected in the Galton Laboratory. Although many of his papers have gone astray, some computer print‐outs have been saved. In view of the work he had put into these, the natural importance of the subject, the generous support given to him by the Medical Research Council, and the affection of his many friends, it would seem worth while publishing these results. No doubt he himself would have presented them differently; but the following paper attempts to set them out fairly. I am grateful for help, suggestions, and criticism from Professor H. Harris, Dr C. J. Hilditch, and especially from Professor W. J. Ewens, and also to Dr W. J. Hamilton who has succeeded in saving some of Dr Price's incomplete manuscripts. CEDRIC A. B. SMITH
The frequency in Japanese of genetic variants of 22 proteins
Authors: FERRELL R. E. , UEDA N. , SATOH C. , TANIS R. J. , NEEL J. V. , HAMILTON H. B. , INAMIZU T. , BABA K.
Published: September 2007

This paper presents the results of an electrophoretic survey of approximately 4000 individuals from the cities of Hiroshima and Nagasaki, Japan, for four serum proteins: albumin, ceruloplasmin, haptoglobin and transferrin. The haptoglobin gene frequencies obtained for the HP1‐HP2 polymorphism are in agreement with earlier reports. Rare electrophoretic variants of albumin, ceruloplasmin and haptoglobin occur with frequencies of 2.48, 0.50 and 0.58 per 1000 determinations, respectively. The noteworthy finding of 8 distinct transferrin variants in these populations, with a combined frequency of 20.90 per 1000 determinations, is also presented. Four of these variants (DCh1, B1, B3 and Dhir2 which corresponds electrophoretically to D4) have been reported in other populations in Japan, but the other five have not previously been differentiated.
The frequency in Japanese of genetic variants of 22 proteins III. Phosphoglucomutase‐1, phosphoglucomutase‐2, 6‐phosphogluconate dehydrogenase, adenylate kinase, and adenosine deaminase
Authors: SATOH C. , FERRELL R. E. , TANIS R. J. , UEDA N. , KISHIMOTO S. , NEEL J. V. , HAMILTON H. B. , BABA K.
Published: September 2007

Five enzyme systems, PGM1, PGM2, ADA, 6‐PGD and AK, were examined by electrophoresis in over 4000 samples from Hiroshima and Nagasaki for the frequencies of common and rare variants. In the PGM1, system, the PGM21 allele and PGM71; allele were found in polymorphic proportions. I n addition, five kinds of slow variants and three types of fast variants of PGM1 were detected. The PGM3 NGS 11 allele was found in five individuals from Nagasaki, but was not observed in samples from Hiroshima. There were no variants of PGM2. Three kinds of fast variants of 6‐PGD were detected. NO variation in AK was observed. There were no rare variants of ADA. The 6‐PGDc allele had a frequency of 0.084 in Hiroshima, and 0.093 in Nagasaki, and the ADA2 allele frequencies of 0.025 in Hiroshima and 0.032 in Nagasaki.
Maternal age, parity* social class and sex ratio
Authors: ROSTRON JOHN , JAMES WILLIAM H.
Published: September 2007

SUMMARY AND CONCLUSIONS:

1. Analysis of variance has been performed on data on more than 1 million Scottish births simultaneously classified by sex, maternal age, birth order and social class.

2. Although there is a, probably significant mean shift in the sex ratio with social class, the fluctuation between years, age‐classes and parity‐classes are very large in comparison. The shift is in the expected direction, viz. higher in the upper social classes and lower in the lower social classes.

3. Data have been cited, and fresh data accumulated, on very large samples of white U.S. live births (each of more than 20 million births). These suggest that there is a small decline in sex ratio independently and significantly with both maternal age and birth order.

4. In general, the decline with maternal age cannot be detected in U.S. samples representing only one year's births (numbering roughly 3 million births).

5. It seems reasonable to suppose that the causes of such declines may be present in the Scottish data, but that their effect has been swamped by sampling error.

6. The most important result in the present study is the failure to detect any meaningful association between sex ratio and social class.

7. It is inferred that if there is such an association in white births, it is not very large and therefore cannot be responsible for bias in the data of Garfinkel and Selvin.

8. Accordingly it is argued that the decline in sex ratio with paternal age detected by these authors and others may be real rather than a statistical artifact.

9. Such an association would be compatible with the hypothesis that the sex of EL human zygote is somehow dependent on timing of insemination and hence on coital rate.
F‐statistics and analysis of gene diversity in subdivided populations
Authors: NEI MASATOSHI
Published: September 2007

It is shown that Wright's F‐statistics can be defined as ratios of gene diversities of heterozygosities rather than as the correlations of uniting gametes. This definition is applicable irrespective of the number of alleles involved or whether there is selection or not. The relationship between F‐statistics and Nei's gene diversity analysis is discussed.
Bioassay of kinship in northwestern Europe*
Authors: MORTON N. E. , DICK H. M. , ALLAN N. C. , IZATT M. M. , HILI E. , YEE S.
Published: September 2007

Kinship of Barra (Outer Hebrides) is bioassayed as 0.0096 relative to northwestern Europe, in reasonable agreement with prediction of 0.008 relative to Britain. The exponential decline of kinship with distance is similar to Scandinavia. Kinship of larger populations is consistent with predictions from isolates.

Kinship is largely due to local drift rather than Norse admixture, the estimate of which is obscured by drift and appears highly unreliable. Other populations in northwest Europe, including Iceland, Lewis and Orkney, give estimates of kinship which reflect drift and geography, but also do not provide reliable estimates of admixture.

Bioassay of kinship from gene frequencies gives observations to be explained in terms of migration and drift, but contributes nothing to the question of whether polymorphism in the species is maintained by neutral mutation or selection. Although the latter is on various grounds more likely, no calculations based on gene frequency distribution can provide critical evidence.
Lysosomal enzymes in human lymphoblastoid lines: unusual characteristics of RAJI and DAUDI
Authors: SWALLOW DALLAS M. , GARDINER S. ELIZABETH , HARRIS HARRY , ARTHUR ELIZABETH , STEEL C. M. , EVANS H. J.
Published: September 2007

The lysosomal enzymes N‐acetyl hexosaminidase, α‐galactosidase and α‐mannosidase vary in electrophoretic mobility in different human lymphoblastoid (lymphoid) lines. The relative mobilities of these three enzymes and three out of four other lysosomal enzymes tested correlate well with each other. The patterns appear to be relatively stable characteristics of each line. The lines RAJI and DAUDI show a strikingly fast electrophoretic mobility for all of these enzymes. N‐acetyl hexosaminidase is also markedly deficient in DAUDI.
Blue Sepharose chromatography of human alcohol dehydrogenase: evidence for interlocus and interallelic differences in affinity characteristics
Authors: ADINOLFI A. , HOPKINSON D. A.
Published: September 2007

1. The various isozymes of human alcohol dehydrogenase have been examined by Blue

2. The products (α, β1 and γ1) of the common alleles a t the three ADH loci (ADH, ADH, and ADH, respectively) were found to show slight, but significant differences in their aflinities for Blue Sepharose. The order of affinity of the homodimeric isozymes was: aa < ylyl < plP1. The heterodimeric isozymes showed intermediate affinities.

3. The products (γ1 and γ2) of the common alleles (ADH31 and ADH32 respectively) at the ADH, locus showed a pronounced difference in their affinities: the γ1γ1 isozyme was firmly adsorbed by Blue Sepharose, whereas the γ2γ2 isozyme was not adsorbed. The heterodimeric γ1γ2 isozyme was intermediate in its behaviour.

4. The 'usual' and 'atypical' forms of ADH were indistinguishable by Blue Sephasose column chromatography.

5. The 'anodal' form of ADH showed no affinity for Blue Sepharose.

We are grateful to the Department of Pathology, Radcliffe Infirmary, Oxford, for tlie adult post‐mortem tissues and to the M.R.C. Tissue Bank at the Royal Marsden Hospital for foetal specimens. We also thank Mrs Caroline Greensted and Miss Geeta Bulsara for their help and the Wellcome Trust for financial support (Wellcome Trust Research Fellowship for Dr A. Adinolfi).
Developmental changes in the protein profiles of human cardiac and skeletal muscle
Authors: TIPLER T. D. , EDWARDS Y. H. , HOPKINSON D. A.
Published: September 2007

1.The use of SDS electrophoresis as a tool for the analysis of developmental processes in man has been evaluated.

2. The protein profiles of cardiac and skeletal muscle from foetal (10–24 weeks gestation) infant and adult specimens have been analysed and striking developmental changes were found which involved all the major proteins.

3. Before 20 weeks gestation the soluble protein profile of skeletal muscle appears to consist largely of extracellular proteins.

4. Myoglobin was found in foetal cardiac muscle from 20 weeks gestation but was not demonstrable in foetal (< 24 weeks gestation) skeletal muscle. Foetal and adult myoglobin were indistinguishable.

5. A limited survey of the protein patterns of brain, liver and kidney was carried out. In general these tissues show less developmental change than skeletal or cardiac muscle.

We are grateful to the Department of Pathology, Itadcliffe Infirmary, Oxford, for the adult post‐mol ten1 tissues and to the MRC Tissue Bank a t the Royal Marsden Hospital for foetal specimens. We also tllank Mrs Caroline Greenstead for her help.
The frequency in Japanese of genetic variants of 22 proteins: V. Summary and comparison with data on Caucasians from the British Isles
Authors: NEEL J. V. , UEDA N. , SATOH C. , FERRELL R. E. , TANIS R. J. , HAMILTON H. B.
Published: September 2007

The frequencies in Hiroshima and Nagasaki of rare variants (represented in less than 2 % of the individuals surveyed) is summarized for a series of 22 proteins (25 polypeptides). The average number of persons examined for each protein was 3312. There are three pairs of homologous proteins in the series: PGM, and PGM, CA I and CA 11, and HGB A and A,. Only for the first pair is there a significant difference between the two in the total frequency and number of different kinds of variants; it is suggested this may reflect differences in the mutation rates of the corresponding structural genes. For 23 of these polypeptides, comparable data are available for British Caucasians. The average frequency of variants for loci in common in the two series is 2.0/1000 person determinations for Japanese and 1.6/1000 for Caucasoids. At two loci (PGMl and PHI) there were significantly more variants in Japanese than in British; these two loci account for the greater average frequency of variants in Japanese. However, a conservative comparison of number of diflerent variants (electromorphs) encountered, using the 0 statistic of Ewens (1972), yields no significant difference for any of the 22 possible contrasts. The potential usefulness of data of this type in reaching conclusions regarding comparability of mutation rates in two populations is discussed. For the present, the fact that one electromorph may shelter multiple different amino acid substitutions in a protein limits the inferences to be drawn from such contrasts.

It is 8 pleasure to acknowledge our indebtedness to Dr Peter Smouse and Dr Warren Ewens for statistical consultations, but responsibility for the tentative interpretations is entirely our own.
On data and methods in investigations on parental‐age effects Comments on a paper by J. D. Erickson
Authors: STENE JON , STENE EEVA
Published: September 2007

An analysis of the NIS data used by Erickson (1 977) has revealed that this data contains too few Down' syndrome cases with older fathers. Thus the data is less suited for an investigation of a possible paternal age effect. In addition, the statistical tests used by Erickson have low power, so that they are unable to detect a moderate paternal‐age effect.

Our analysis has demonstrated that discussions on paternal‐age effects and similar problems should be based on high‐quality data. The investigation is better based on a small high‐ quality material than on a large one with serious underascertainment. In the latter case one has to be extremely careful because the missing observations nearly always have common characteristics which may cause serious bias of relevant kinds.

The work haa been supported by the Danish Medical Research Council.
On measuring genetic distance by selection intensity
Authors: CHUN LI CHING
Published: September 2007

A simple selection model (fitness 1, w, w2 for AA, Aa, aa) is employed to change the gene fre‐ quency of one population to another. The genetic distance is then defined as d = ‐log w between the two populations. The distance is symmetrical with respect to the two populations. It is additive: d, = dI2+d23. The sampling variance of d takes a very simple form. The possible difficulties of using genetic distance in studying evolutionary history have been briefly discussed. The writer means no offence to those who have developed or used the various measures of genetic distance.
Heritability of stature in a West African population
Authors: ROBERTS D. F. , BILLEWICZ W. Z. , McGREGOR I. A.
Published: September 2007

Heritability of stature in a West African popuIation is calculated from longitudinal data collected over 26 years. Statistical and analytical difficulties encountered in the study include those due to variation in stature with age, sex, recording and measuring, variation in number of offspring, variation in number of spouses, and heterogeneity of within‐sibship variances.

The structure of the population allows a half‐sib analysis which is particularly useful in interpretation of the intrafamilial correlations and regressions. The heritability estimate of 0.6 appears lower than that from studies in European populations, The environmental contribution t o the stature variance is pronounced, but is not unexpected in the light of the rigours of the traditional way of life in West African surroundings.

Acknowledgement is gratefully made to Miss R. M. Holliday for computational assistance.
An incorrect definition of fitness revisited*
Authors: DENNISTON CARTER
Published: September 2007

I have attempted to show that a certain mistaken definition of fitness, which surfacesoccasionally, may turn out to have some merit. No claim is made that it is an improvement on, or should replace, the conventional definition of fitness; but it is different and has its own validity. Its generality is intriguing, its application is not limited either to selection or one locus models, and it may be easier to measure experimentally.

The author wishes to express his thanks to Professors James Crow and Thomas Nagylaki and Mr William Engels for their most helpful comments and criticisms. Engels for their most helpful comments and criticisms.

This research was sponsored by the National Institutes of Health (grant GM15422 09).
Parental age and birth order in the aetiology of some sex chromosome aneuploidies
Authors: CAROTHERS A. D. , COLLYER S. , de MEY R. , FRACKIEWICZ A.
Published: September 2007

The roles of maternal age, paternal age and birth order in the aetiology of the 47, XXY, 47, XXX and 47, XYY aneuploidies were examined using the liveborn full sibs of propositi as controls. As in previous studies, the incidence of XXY's and XXX's was found to be increased at high parental ages. A small but significant inverse relationship between parental age and the incidence of XYY's was also found. The results were consistent between different methods of ascertainment, different sibship sizes and different years of birth of propositi. The XXY results could not be explained without a maternal age effect and could be explained with a maternal age effect alone. The XXX and XYY results could not be explained without either a maternal or a paternal age effect, but could be explained without a birth order effect. Estimates of the relative risk at different parental ages are derived and shown to apply to the general population, provided the distribution of parental ages at birth is the same for those parents who are at risk (and who may or may not comprise the entire population) as for those who are not. The validity of the method of analysis was confirmed by applying it to a group of familial chromosome rearrangements which, as expected, revealed no dependence on parental age or birth order.
Rapid computer analysis of linkage data
Authors: STURT ELIZABETH
Published: September 2007

A well tested and useful computer program for screening large amounts of pedigree data for linkage is described. All types of pedigree and genetic systems with up to six alleles present in the pedigree are allowed. An original procedure fills in uncertain genotypes and searches for internal inconsistencies in the data and is extremely thoroughgoing. Population gene frequencies are not used, although the program does take account of rare alleles. The scoring method is based on the division of the pedigree into sibships and the application of z‐scores for the sexes considered separately wherever possible. About 2000 pedigrees have been analysed and scores for about the same number of pairs of loci are on tape.

A mathematical exercise showed that the method of z‐scores with score corrections, which is very much quicker than calculating complete likelihood, is acceptably efficient and its efficiency approaches 100% when scoring rare recessive systems.

It is shown that the maximum value of the score is a good criterion for linkage, values of 3.1 and 4.0 indicating roughly 95% and 99% probabilities of linkage. The calculation of 2‐unit support limits for the estimate of the recombination fraction between linked loci is advocated, and tables of these are given for syntenic loci. No new linkages were confirmed.
α‐Galactosidase isozymes in normal individuals, and in Fabry hemizygotes and heterozygotes
Authors: SØRENSEN S. A. , HASHOLT LIS
Published: September 2007

A method for staining of α‐galactosidase with the synthetic substrate a‐naphthyl‐α‐galacto‐pyranoside after isoelectric focusing on gel slabs has been devised. Depending on the method used for cell extraction, at least seven isozymes could be detected in cell extracts of cultured fibroblasts from normal individuals.

Thermal treatment revealed that both heat‐stable and heat‐labile isozymes occur in normal fibroblasts. The heat‐IabiIe isozymes were not detected in cells from Fabry hemizygotes and thus truly reflect products of the a‐gal A locus. Three heat‐stable isozymes observed in normal individuals were also found in Fabry heterozygotes and hemizygotes and are presumably determined by the α‐gal B locus. The remaining isozymes were stained very weakly in the hemi‐zygotes and were heat‐stable. The relation of these isozymes to the A or B locus is uncertain. After treatment with neuraminidase the =I‐gal A isozymes could not be detected and one of the α‐gal B isozymes appeared broader.

The isozyme pattern observed in heterozygotes was almost identical to the normal one.
The effect of social selection on the population dynamics of Huntington's disease
Authors: YOKOYAMA SHOZO , TEMPLETON ALAN
Published: September 2007

Wallace (1976) postulated the importance of social selection on the frequency of Huntington's disease. This effect of social selection was studied with respect to the population dynamics of Huntington's disease genes. It is shown that social selection operates mainly through heterozygotes. Existing data indicate that the frequency of Huntington's disease in the population is determined by its social effects.
Tooth sizes in two males with deletions of the long arm of the Y‐chromosome
Authors: ALVESALO L. , CHAPELLE A. DE LA
Published: September 2007

Permanent and deciduous tooth crown sizes in two males with deletions of the long arm of the Y chromosome and their first‐degree relatives were examined. The first proband with a deletion in the proximal part of Yqll showed definitely smaller teeth than his father or population control males. The second proband with a deletion in the distal part of Yqll showed large or normal sized teeth compared to his brother or population control males. These data support the results of earlier studies indicating a promoting effect of the Y chromosome on tooth growth, and suggest that the location of the growth‐promoting gene(s) is in Yqll. It is postulated that statural growth is affected by the same gene(s).
Complementation analysis of human sialidase deficiency using natural substrates
Authors: SWALLOW D. M. , HOOGEVEEN A. T. , VERHELJEN F. W. , GALJAARD H.
Published: September 2007

Complementation analysis by somatic cell hybridization to produce heterokaryons has shown that at least three complementation groups exist within the disorders in which the enzyme sialidase is deficient. We have confirmed these results by electrophoretic analysis of two glycoprotein enzymes, adenosine deaminase and acid phosphatase, which show aberrant electrophoretic mobilities in these disorders. These abnormal forms, which have excess sialic acid bound, disappear on complementation and are replaced by normal mobility components. It is suggested that the sialidase produced on complementation uses the abnormal forms as natural substrates and that they may represent normal intermediates in the processing of glycoprotein enzymes.
Chromosomal localization of a single copy gene by in situ hybridization ‐ human β globin genes on the short arm of chromosome 11
Authors: MALCOLM S. , BARTON P. , MURPHY C. , FERGUSON‐SMITH M. A.
Published: September 2007

1. The localization of the β globin genes by in situ hybridization to fixed chromosomes is described.

2. The probe used was a [3H]cRN A copy of a genomic clone containing in total 4‐4 kb of DNA and including the β globin gene.

3. The evidence for the localization of the gene comes from three pieces of data, (a) Chromosome 11 is labelled to double the extent expected if the grains were randomly distributed, (b) the extra grains above background are clustered on the short arm of 11 close to the centromere, and (c) the absolute number of grains observed is very close to that predicted for a probe of that length by comparison with ribosomal genes. The localization is in agreement with that obtained by other methods.

4. This method could be extended to any gene for which a genomic clone containing at least 5 kb of single copy DNA is available.
Linkage relationship of the loci for Anderson‐Fabry disease and the Xg blood groups
Authors: JOHNSTON A. W. , SANGER R.
Published: September 2007

Information provided by the follow‐up of a family in which Anderson‐Fabry disease segregates, together with a family reported by Ropers et al. (1977), negates the previous evidence of a probable linkage between αGALA and Xg.
Estimation of fitness reduction due to a chronic disease in man
Authors: NEI M. , YOKOYAMA S.
Published: September 2007

An improved mathematical method is presented for estimating the amount of fitness reduction due to a chronic disease by using demographic data. It is shown that Cavalli‐Sforza and Bodmer's equivalent formula gives an underestimate. Application of the new formula indicates that the selective difference between blood groups 0 and A, resulting from their association with duodenal ulcer, is 6‐4 times 10‐5, i.e. ten times higher than Cavalli‐Sforza and Bodmer's estimate.
Genetics of paraoxonase
Authors: EIBERG H. , MOHR J.
Published: September 2007

Danish family material comprising 1664 unrelated individuals (parents) and 3169 children, as well as 699 grandparents of the same families, were examined for paraoxonase activity. A micro‐autoanalyser method, comprising a primary testing in tris buffer at pH 7‐5 and, in the case of primarily intermediate individuals, a secondary testing at pH 10, was applied. This gave a better discrimination than testing only at pH 7.5, because individuals around the low mode of the primary activity distribution had their pH optimum at pH 10, while the optimum of individuals around the high was at pH 8.5. By this combined testing all individuals could be unequivocally classified as ‘low’ or ‘high’, and the family material was compatible with the low phenotype representing homozygosity for an autosomal recessive gene with a frequency Plow= 0–726. Out of 5532 individuals, 5 showed an almost complete lack of paraoxonase activity.
Immunoglobulin heavy chain genes in humans are located on chromosome 14
Authors: HOBART M. J. , RABBITTS. T. H. , GOODFELLOW P. N. , SOLOMON E. , CHAMBERS S. , SPURR N. , POVEY S.
Published: September 2007

The human immunoglobulin heavy chain gene complex has been assigned to chromosome 14 by filter hybridization of restriction digests of mouse‐human somatic cell hybrids. Cloned DNA probes for both variable and constant regions were used.
Regulation of expression of liver‐specific enzymes: I. Detection in mammalian tissues and cultured cells
Authors: KIELTY C. M. , POVEY S. , HOPKINSON D. A.
Published: September 2007

Nineteen enzymes showing highest activity in liver were examined in human and rodent tissues and cultured cells using starch‐gel electophoresis. The rat hepatoma line Faza 967 strongly expressed 13 of these enzymes. A series of somatic cell hybrids, constructed between Faza and cells of non‐hepatic origin derived from man or from Chinese hamster, were examined for expression of these enzymes. Some of the human/rat hybrids continued to produce rat liver specific enzymes, and the human forms of the enzymes glutamate‐pyruvate transaminase, a‐glycerophosphate dehydrogenase, alcohol dehydrogenase and pyruvate kinase L were re‐expressed in a few cases.
Genetic heterogeneity of human prothrombin (FII)
Authors: BOARD P. G. , COGGAN M. , PIDCOCK M. E.
Published: September 2007

A new procedure for the electrophoresis and localization of prothrombin is described. This technique has revealed three allelic variants at the prothrombin structural locus (FII). One of these alleles (F II4) reaches polymorphic frequencies in some Pacific Island populations.

Investigation of the activated products of the three variant prothrombins has demonstrated that, in each case, the structural variation is located on a profragment and not on the enzymically active thrombin molecule.
Human mitochondrial glycerol phosphate dehydrogenase (GPDM) isozymes
Authors: SHAW M. A. , EDWARDS Y. H. , HOPKINSON D. A.
Published: September 2007

A hydrophobic/phospholipid electrophoretic system has been devised which makes possible the analysis of human mitochondrial glycerol phosphate dehydrogenase (E.C. 1.1.99.5, GPDM.

GPDM has a wide tissue distribution in both adult and foetal life and is active in cultured lymphoblastoid cells and fibroblasts but is absent from red cells.

The solubilization procedure does not significantly alter the kinetic properties of the enzyme (Kmα‐glycerophosphate = 0.04‐0.07 m, Km PMS = 0.19‐0.35 mm) but the soluble form is less thermostable.

Comparisons of physicochemical characteristics, tissue distribution and coenzyme requirement point to a separate genetic determination and low level of evolutionary relatedness between GPDM and its cytosolic counterpart GPDs.