bluuebunny/crossref_metadata_2025 huggingface dataset:
On effects of relaxed selection in familial disorders
Authors: DAVIE A. M. , SMITH C. , CURNOW R. N. , HOLLOWAY S. M.
Published: September 2007

Theoretical predictions are made of the effect of improved treatments, with consequent increase in fertility of affected individuals, on the frequency of familial disorders. Multifactorial inheritance and some two‐locus models are considered. (Changes for simple Mendelian disorders have been estimated previously by many authors.) It is estimated that, with two‐locus or multifactorial models, an increase in frequency per generation of not more than a few per cent of the frequency of a disorder may be expected. The greatest increase will be in the first generation following introduction of the new treatment.

A. M. Davie is a Medical Research Council Training Fellow.
On the probability of demonstrating differential fertility in genetic studies
Authors: MacCLUER JEAN WALTERS
Published: September 2007

Computer simulation has been used to investigate the probability of detecting genetic dif‐ ferences in fertility in small cohorts. It was found that in cohorts of size 200 which have the demographic characteristics of females born in the United States in 1921‐5, the probability is approximately 0.50 of detecting, by analysis of variance, either a 20 yo reduction in the monthly probability of conception or a 15–20 yo increase in the rate of foetal loss in the first month after conception. Consideration is given to the relative sensitivities of various observable measures of fertility to variation in underlying fertility components.

This study was supported by U.S. Public Health Service Grant 1 R01 HD07618 and by a Biomedical Research Support Grant from the National Institutes of Hoalth. I wish to thank Ellen R. Brennan for assistance in surveying the fertility literature; Bennett Dyke for helpful criticism of the manuscript; and the Center for Advanced Study in the Behavioral Sciences for providing me with the opportunity to complete this study. My fellowship at the Center was funded by National Science Foundation Grant BNS76‐22943.
Characteristics of simple sibship variance tests for the detection of major loci and application to height, weight and spatial performance
Authors: Fain P. R.
Published: September 2007

Simple methods have been proposed as screening tests for major loci. These methods rely primarily upon the detection of differences in within sibship variances expected for segregating and non‐segregating sibships when a major locus is present. In the present study, computer simulation was used to investigate power and robustness of the test statistics. Power of the analyses depends upon the specific major locus model, but, in general, their application is quite practical for small samples. The test statistics were shown to be sensitive to deviations from normality, but robust under the conditions of either a polygenic or environmental model. Application of the test procedures to sibship data from the Boulder Family Study led to significant results for a three‐dimensional spatial rotation test, but results for height and weight were non‐significant. The simplest interpretation of the results for the spatial performance test wasin tcrms of a sex‐linked major locus.
Partial trisomy 13 presumably due to recombination in an inversion heterozygote and by unequal crossing‐over
Authors: KOSKE‐WESTPHAL THEA , PRUSZAK‐SEEL ROSWITH E. , NISS R. , PASSARGE E.
Published: September 2007

Two unrelated infants with partial trisomy 13 for the distal half of the long arm are described. In one, a familial pericentric inversion is present in three generations and crossing‐over in the inversion loop is considered as cause of partial trisomy 13. The other showed a tandem duplication of the distal half of the long arm of chromosome 13 beyond 13q14. This is interpreted to have arisen by unequal crossing‐over in mispaired synapsis.

It is suggested that recombination rather than breaks is a distinctive although rare cause of human chromosomal imbalance.
A possible mutation of a fluorescence polymorphism
Authors: ROBINSON J. A. , BUCKTON K. E. , EVANS H. J. , ROBSON E. B.
Published: September 2007

The segregation of the Q‐band polymorphisms in 32 families have been studied. From 90 matings in these families, there were a total of 208 offspring. In one of these offspring it could be shown that there had been a change of a fluorescent polymorphism, resulting in the loss of fluorescent intensity in the satellite of a chromosome 21. The origin of such a ‘mutation’ and a consideration of mutation rates is discussed.
Genetic linkage relation of the pepsinogen Pg5 locus
Authors: KORSNES L. , T. GEDDE‐DAHL Jr.  , OLAISEN B. , THORSBY E. , OLVING J. , SIVERTS A. , BRATLIE A.
Published: September 2007

Linkage relations between pepsinogen Pg5 and 28 genetic marker loci have been analyzed in Norwegian families. No strong hint of linkage was found. Linkage to Pg5 in males has been ruled out below 25% recombination for HLA and GPT, below 20% recombination for Rh, PGM1, ACP, Gc, MNSs, PGM3, and Gm and Pi, below 15% recombination for Hp, below 10% recombination for Fy, ABO, C3 and Jk and below 4% for Kell, Tf, C6, Km and Le(Se). Possibilities of loose linkages include Pg5‐C6 and Pg5‐MNSs, both of which should be followed up.
The applicability of the Hardy‐Weinberg principle in the study of populations
Authors: SCHAAP T.
Published: September 2007

The applicability of the Hardy‐Weinberg principle in the analysis of a theoretical population under directional selection is assessed. It can be shown that the analysis of genotype frequencies by the conventional method can never reveal the existence of directional forces. Consequently, a population actually in transient polymorphism may seem to be either in Hardy‐Weinberg equilibrium or subject to balancing or disruptive forces. Therefore, population studies should not be based on genotype frequencies at a single point in time.
Biochemical genetics of the pentose phosphate cycle: human ribose 5‐phosphate isomerase (RPI) and ribulose 5‐phosphate 3‐epimerase (RPE)
Authors: SPENCER N. , HOPKINSON D. A.
Published: September 2007

1. Staining procedures are described for the detection after starch‐gel electrophoresis of ribose‐5‐phosphate isomerase (RPI) and ribulose 5‐phosphate 3‐epimerase (RPE).

2. Both RPI and RPE were detected in all human tissues including red cells, lymphocytes and fibroblasts.

3. No evidence was found for more than one structural gene locus for either enzyme.

4. NO allelic variants of either enzyme were found in erythrocyte lysates from over 200 unrelated individuals.

5. Preliminary data are presented which suggest that differences in tissue RPE isozyme patterns may be due to endogenous proteolytic activity.

6. Electrophoretic analysis of RPE and RPI isozyme patterns in extracts of man/mouse hybrid cells indicates that RPE is probably a dimer and RPI may also be polymeric.
Expression of GALT in 9p chromosome alterations: assignment of GALT locus to 9cen→9p22
Authors: SPARKES R. S. , SPARKES M. C. , FUNDERBURK S. J. , MOEDJONO S.
Published: September 2007

Determination of activity and electrophoretic mobility of GALT in patients with various chromosome 9 deletions and duplications confirms the assignment of its locus to 9p and suggests its locus is in the segment 9cen→p22. Two inversions of 9qh (inv(9)(pllql2)) did not alter GALT expression.
Assignment of a human diaphorase (DIA4) to chromosome 16
Authors: POVEY S. , WILSON D. , EDWARDS Y. H.
Published: September 2007

A human FAD‐dependent diaphorase, DIA4, has been studied in 29 independent human‐rodent hybrids and in 17 subclones. The results suggest that the locus DIA, is on chromosome 16.
On tune deafness (dysmelodia): frequency, development, genetics and musical background
Authors: KALMUS H. , FRY D. B.
Published: September 2007

143th the aid of the Distorted Tunes Test a group of British adults could be established whose melodic aptitude was below a certain level and whom we called tune deaf. They are only a fraction of those popularly called tone deaf. The Distorted Tunes Test is only slightly correlated with pitch discrimination, short term tonal memory or number memory. In children ability to pass the Distorted Tunes Test develops at greatly varying speeds and to a varying degree, reaching stability in adolescence. Tune deafness has a familial distribution and segregates in away suggesting an autosomsl dominant brait with imperfect penetrance. Some degree of positive assortatire mating has been established.
A two locus model for juvenile diabetes
Authors: THOMSON GLENYS
Published: September 2007

As stated before, the aim of this analysis was t o determine if a two locus plus environment disease model for IDDX mould give predicted values of various population parameters in agreelllent with observed values, or whether the model could be ruled out by obvious discrepancy between sonie predicted and observed values. It is assumed that the HLA linked ‘;disease’ allele D, follows a recessive mode of inheritance, with an allele frequency of approximately 357;. The results show that the addition of a second ‘disease’ locus gives predicted values that, are certainly not in disagreement with observed values. This in no way proves that this is the mechanism operating with IDDN but certainly makes it a feasible possibility.

The discrepancies with observed population parameters of the one locus plus environment dominant and recessive models, plus the discrepancy between concordance rate in monozygous twins and incidence in sibs of probands, plus the observations of association of the Lewis blood group with IDDX, provide evidence in favour of the present two locus model. At the moment no real distinction can be made as t o whether it is more likely that the hypothesized second ‘disease’ locus would follow a dominant or recessive mode of inheritance.

A further point of interest from the study by Vague et al. (1978) is the demonstration that not only IDDSI but also maturity onset diabetes shows an association with the Lewis negative blood group. This opens up exciting possibilities concerning the relationship of the two diseases. It may be that susceptibility to maturity onset diabetes is determined either solely by one locus (D2) or by D, plus other loci, plus environmental effects, while susceptibility to IDDM is determined by two (or possibly more) loci (D1 and D,) plus environmental effects. The observation by MacDonaltl(1974) of an equal incidence of maturity‐onset diabetes among the ancestors of juvenile‐diabetics and non‐diabetics would argue against such an hypothesis. However, further investigation of this question is called for in view of Vague et al (1978) observation.

Obserx‐ations from the mouse are also supportive of the involvement of more than one locus in determining the degree of severity of diabetes. Coleman (1978) states that in the mouse, ‘The severity and clinical course of the diabetes produced depends on the interaction of the mutant, gene with the inbred background rather than the action of the gene itself. Thus on one genetic background a well‐compensated, maturity onset type diabetes, compatible with nearnormal life is observed whereas on another inbred background the syndrome presents as a juvenile‐type diabetes with insulinopenia, islet cell degeneration, marked hyperglycaemia, sonie ketosis and a much shoxtened lifespan.’ I n these studies the diabetic ‘disease’ locus being studied follows a recessive mode of inheritance and ‘the modifiers leading to islet hypertrophy and well‐compensated diabetes compatible with a near normal lifespan are dominant to those factors causing severe diabetes’ (Coleman, 1978).
Polymorphism of human C5
Authors: HOBART M. J. , GUEDES M. A. VAZ , LACHMANN P. J.
Published: September 2007

C5 is polymorphic in Melanesians and related peoples. The polymorphism is demonstrated by isoelectric focusing and functional detection. Inheritance is autosomal and codominant. Preliminary linkage data suggest that C5 is not close to HLA.
Activity of adenosine deaminase allelic forms in intact erythrocytes and in lymphocytes
Authors: BATTISTUZZI G. , IUDICONE P. , SANTOLAMAZZA P. , PETRUCCI R.
Published: September 2007

The distribution of ADA activity has been studied for ADA 1 and ADA 2‐1 individuals in intact and lysed erythrocytes and in lymphocyte lysates.

ADA activity in intact RBC is 20‐30% lower than in lysates, in lymphocytes it is 10 times higher.

The difference between ADA 1 and ADA 2‐1 mean enzyme activities which we previously described in RBC lysates has been found also in intact RBC and in lymphocyte lysates.
Natural selection associated with birth weight I. Selection intensity and selective deaths from birth to one month of life
Authors: TERRENATO L. , GRAVINA M. F. , ULIZZI L.
Published: September 2007

Differential mortality as a function of birth weight was studied up to the 4th week of life in all single births in Italy in 1974.

Both selection intensity and selective mortality are much higher with increasing immaturity.

For babies born at term or after 8 months of pregnancy selection intensity tends io relax as early as one week after birth, while for those born after 7 months selection is at work for a longer period.

Selective mortality, on the other hand, keeps increasing after birth but its relevance is relatively decreasing since average mortality after birth continues to decrease.
New genetic variants of glucose 6‐phosphate dehydrogenase (G6PD) in Italy
Authors: SANSONE G. , PERRONI L. , TESTA U. , MARENI C. , LUZZATTO L.
Published: September 2007

Six new variants of human erythrocyte G6PD have been characterized. All of them were found in Italian males and all were associated with enzyme deficiency, but only two with signs of haemolysis. These and other variants reported in the literature, which must thus far be regarded as sporadic, are found to map in parts of Italy where common types of G6PD deficiency are also prevalent.
Mapping by gene dosage, using aneuploid human lymphoid cell lines
Authors: SOOS M. , SHADE M. , BELL H. , MOXLEY M. , STEEL C. M.
Published: September 2007

Human lymphoblastoid cell lines evolve in vitro by the emergence of successive waves of clones which are often chromosomally marked. This offers the opportunity to compare tissue samples of the same genetic origin but differing in certain defined parts of the karyotype.

Using selected sets of lines in which the members of genetically matched pairs differed in the number of copies of 8p or of 12p, levels of GSR and LDH B respectively have been shown to correlate with the specific chromosome aberrations, supporting existing data on the regional assignment of these two structural loci.

This approach represents a useful addition to established methods for human gene mapping.
Growth, DNA repair, sister chromatid exchange and chromosome studies in fibroblasts fromHuntington's disease patients
Authors: DELHANTY J. D. A. , PARRINGTON J. M. , CASEY G. , ATTWOOD J. , WEST L. , KIRK D. , CORNEY G.
Published: September 2007

Fibroblast cultures from six unrelatedHuntington's Disease (HD) patients and controls and one affected relative of an HD patient were used in studies of cell growth, DNA repair, sister chromatid exchange (SCE) and chromosome aberrations.

There were no significant differences in background levels of SCEs or of chromosome aberrations between HD cultures and controls.

Preliminary results using epidermal growth factor indicated that HD cells may have a lowered relative response to this polypeptide hormone.

Cell growth studies showed no correlation between growth rate and HD.

Increased cell saturation density was recorded in cell lines from four of the HD patients; the remaining three lines from affected individuals (two of them related) were indistinguishable from control cultures. This variation may reflect genetic heterogeneity in HD.

An apparent deficiency in DNA repair capacity following UV irradiation in cultures from three HD patients was subsequently shown to be the result of the increased cell saturation densities in these cultures.
Family studies on nucleoside phosphorylase and the short arm of chromosome 14
Authors: COOK P. J. L. , ROBSON E. B. , ROGERS P. A. , NOADES J. E. , BUCKTON K. E. , WATSON A. R.
Published: September 2007

A family with two nucleoside phosphorylase‐deficient patients has been scored for the segregation of NP0 and the variable region 14p. The most likely 14p: NP recombination fraction is (M5 in males and 0–30 in females.

There is no family data to assign the Pi:Gm linkage group to chromosome 14, but as immunoglobulin heavy chain has been assigned to this chromosome by somatic cell methods the most likely gene order is 14p:NP: Pi:Gm with Pi in 14q2 and Gm in 14(q23 →q32), but the order 14p:NP:Gm:Pi with Pi in 14(q24 → qter) and Gm in 14(q22 → q24) is not excluded.

The available linkage data between biochemical markers on acrocentric chromosomes and their short arm markers suggest that there may be more recombination towards the ends of human chromosomes whether or not those ends carry centromeres.
HLA genotype distribution and genetic models of insulin‐dependent diabetes mellitus
Authors: SVEJGAARD A. , RYDER L. P.
Published: September 2007

When comparing the odds ratios (OR's) obtained by contrasting various HLA‐DR phenotypic classes in patients (e.g. diabetics) and controls, it is desirable to use the same reference phenotypes for all OR's. If this is done, it can be shown that the OR for, say, DR3/4, heterozygotes cannot exceed the OR's for both of the two homozygotes (DR3/3 and DR4/4), if there is one disease susceptibility locus with one normal allele and one susceptibility allele in linkage disequilibrium with two HLA‐DR alleles {HLA‐DR3 and 4) and if the action of the susceptibility gene is dominant, recessive or intermediate between dominant and recessive. In each of these cases, the OR for the heterozygotes will be intermediate between the OR's of the two homozygotes. If the two alleles at the susceptibility locus act in an overdominant way, the OR for the heterozygotes may in some cases exceed the OR's of both homozygotes. Comparison of the magnitude of two OR‐values can be reduced to investigating whether the OR value generated by comparing one phenotypic class against the other (as reference group) differs from unity. There is suggestive but not conclusive evidence that the OR of developing insulin‐dependent diabetes for the DR3/4 genotype is higher than the corresponding OR‐values for both of the two homozygotes (DR3/3 and DR4/4), indicating that the susceptibility to this disease may not be explained by a dominant, recessive or intermediate model.
Confirmation of linkage between antithrombin III and Duffy blodd group and assignment of AT3 to 1q22 → q25
Authors: WINTER J. H. , BENNETT B. , WATT J. L. , BROWN T. , ROMÁN C. SAN , SCHINZEL A. , KING J. , COOK P. J. L.
Published: September 2007

Linkage studies on two families segregating for antithrombin III deficiency confirm the linkage between AT3 and the Duffy blood group. The maximum lod score including two published families is +4.2 at recombination fractions around 0.1. Two patients with deletions of 1q have 1/2 levels of antithrombin III suggesting that the AT3 locus lies in bands 1 q22 → 1q25.
The genetic relationship between the human foetal acetylesterase ESA7 and the adult acetylesterase ESA5
Authors: HOPKINSON D. A. , GRIFFITHS J. A. , EDWARDS Y. H.
Published: September 2007

There are very few clear examples among human enzymes of foetal isozymes which are the products of foetal specific gene loci. Earlier studies had pointed to the foetal brain esterase ESA7, as a probable example.

Detailed biochemical investigation of partially purified human adult brain ESA5 and the foetal esterase ESA7 has revealed a close resemblance in the biochemical properties of these two isozymes. In addition to similarities in substrate specificity and inhibition sensitivity the two esterases have the same molecular size (c. 57000), are both relatively unstable at 37 d̀C and show decreased anodal electrophoretic mobility after storage at 20 d̀C. Furthermore there was suggestive evidence that ESA7 and ESA5 may be interconvertible.

A variant esterase isozyme pattern, which shows unusual features of both ESA7 and ESA5, was found in a survey of 120 foetal brains. This variant pattern is consistent with a monomeric structure for both esterases and points strongly to a common genetic determination.
Mapping studies on human mitochondrial glutamate oxaloacetate transaminase
Authors: JEREMIAH S. J. , POVEY S. , BURLEY M. W. , KIELTY C. , LEE M. , SPOWART G. , CORNEY G. , COOK P. J. L.
Published: September 2007

Data from six primary hybrids and twenty‐two subclones have confirmed the assignment of the mitochondrial form of glutamate oxaloacetate transaminase to chromosome 16. Family studies have provided independent confirmation of this and have suggested the gene order PGP‐16qh‐GOT2‐HP. These studies were made easier by the development of a new stain for the detection of GOT activity.
Studies on the genetic and non‐genetic (physiological) variation of human erythrocyte glutamic oxaloacetic transaminase
Authors: WURZINGER K. H. , MOHRENWEISER H. W.
Published: September 2007

The thermostability profile of seven different electrophoretic variants of human erythrocyte GOT found in 13 different, unrelated families from a racially heterogeneous population was examined. The five different slow‐variant and the two different fast‐variant classes could be grouped into four different thermostability classes which were termed unstable, less stable, normal and more stable than normal. The thermostability differences among and within the electrophoretic variant classes permitted differentiation of the 13 individusals possessing an electrophoretic variant phenotype into a total of ten different variants.
Genetic polymorphism of coagulation factor XIIIB subunit in Japanese
Authors: NAKAMURA S. , ABE K.
Published: September 2007

Genetic polymorphism of coagulation factor XIIIB subunit in Japanese has been described, using thin‐layer agarose gel isoelectric focusing followed by immunofixation.

Phenotypes of factor XIIIB subunit were essentially classified into three common patterns A, B and AB. It is estimated that the phenotypes are determined by two codominant alleles. A new rare variant B' has been detected in Japanese.

Gene frequencies calculated from 304 individuals showed FXIII‐BA=0.735, FXIII‐BB= 0.252 and FXIII‐BB'= 0.013, respectively. The distribution of phenotypes fitted the Hardy‐Weinberg equilibrium.
The use of fluorogenic peptide substrates for the detection of coagulation factors II and X after electrophoresis
Authors: BOARD P. G.
Published: September 2007

The use of synthetic oligopeptides with a fluorescent detector group for the localization of thrombin and activated factor X activity after electrophoresis is described. This new technique provides high specificity and resolution. This approach to the detection of blood coagulation factors II and X can be extended to other factors, where their specific peptide cleavage sequence is known.
A monoclonal antibody recognizing a cell surface antigen coded for by a gene on human chromosome 17
Authors: BAI Y. , SHEER D. , HIORNS L. , KNOWLES R. W. , TUNNACLIFFE A.
Published: September 2007

The monoclonal antibody, H207, raised against the human T‐cell‐derived acute lymphoblastic leukaemia line HSB‐2, recognizes an antigen of apparent molecular weight 125000 which is coded for by the gene, MIC6, on chromosome 17. Assignment was based on the pattern of reactivity with a panel of somatic cell hybrids. In particular, two hybrids containing only human chromosome 17 or a human translocation chromosome t(3;17) (3pter‐3p11::17p11–17qter) respectively bound H207, whilst their revertands did not. The H207 antigen has a general tissue distribution but is not found on B‐cell lines and is lacking from some T‐cell lines.
Estimating genetic and non‐genetic components of variance for fasting glucose levels in pedigrees ascertained through non‐insulin dependent diabetes
Authors: BEATY T. H. , FAJANS S. S.
Published: September 2007

Fasting glucose levels measured on 337 individuals in 14 pedigrees ascertained through a proband with non‐inuslin dependent diabetes were used to estimate genetic and non‐genetic components of variance under a multifactorial model of inheritance. In this sample genetic factors were important in controlling variation in basal carbohydrate metabolism, as represented by age‐adjusted log‐fasting glucose. There was no evidence that arbitrary sib common environments or arbitrary parent common environments accounted for significant portions of the variability in fasting glucose in these data. An arbitrary environment shared by parent and offspring, however, had a marginally significant impact on the likelihood.

Parameter estimates obtained from multifactorial models analysed in this manner are sensitive to extreme phenotypic values, however, and caution must be exerciese in estimating total genetic variation. While additive genetic factors did account for a significant proportion of the total variation in fasting glucose, a large proportion remained unexplained.
Isozymes of rodent 5‘‐nucleotidase: evidence for two independent structural loci Umph‐1 and Umph‐2
Authors: Swallow D. M. , Turner V. S. , Hopkinson D. A.
Published: September 2007

Two distinct isozymes (UMPH‐1 and UMPH‐2) which hydrolyse pyrimidine 5′‐nucleotides have been identified in mouse, rat and Chinese hamster tissues. One of these, UMPH‐1 appears to be specific for pyrimidine 5′‐nucleotides, whereas the other, UMPH‐2 has a broader substrate specificity. UMPH‐1 and UMPH‐2 show differences in their expression in different tissues. The evidence suggests that UMPH‐1 and UMPH‐2 are coded by distinct structural gene loci, UMPH‐1 and UMPH‐2. These isozymes have not been identified in man, and it is suggested that they may have overlapping electrophoretic mobility.
Sex ratio in spontaneous abortions
Authors: Hassold T. , Quillen S. D. , Yamane J. A.
Published: September 2007

An analysis of sex ratio was made for chromosomally normal and trisomic spontaneous abortions identified in a cytogenetic survey of spontaneous abortions. For the chromosomally normal group, the extent of maternal contamination among 46, XX abortions was determined by comparing chromosome heteromorphisms of the parents with those from the tissue samples. The sex ratio among the normal abortions was then estimated to be approximately 1.30, after correcting for the maternal contaminants and 46, XX hydatidiform moles of androgenetic origin. This estimate is significantly higher than values typically reported for newborns, indicating an effect of X‐linked genes acting in utero.

The sex ratio among trisomic abortions identified in the present study and in four other cytogenetic studies of spontaneous abortions was also significantly greater than 1.0, but not as high as the estimates of sex ratio for the chromosomally normal abortions. There was considerable variability among individual trisomies, and possible mechanisms leading to this variation are discussed.
Natural selection associated with birth weight. IV. U.S.A. data from 1950 to 1976
Authors: TERRENATO L.
Published: September 2007

Differential still birth rates as a function of birth weight have been studied in all single births in the United States of America (White and Non‐white groups) in the years 1950, 1958, 1967 and 1976. During the 26‐year interval a reduction of both the stabilizing effect and the intensity of selection have been observed. For the 1960 cohort it has been found that selection associated with birth weight is mainly operating in the perinatal period and only minor effects are still present at one year of age.
Absence of functional messenger RNA for glycogen phosphorylase in the muscle of two patients with McArdle's disease
Authors: DAEGELEN D. , MUNNICH A. , LEVIN M. J. , GIRAULT A. , GOASGUEN J. , KAHN A. , DREYFUS J. C.
Published: September 2007

(1) Two unrelated cases of McArdle's disease (glycogen storage disease type V, deficiency in muscle‐type glycogen phosphorylase, EC.2.4.1.1) with no detectable inactive protein, and two heterozygous relatives of one patient, have been investigated for the presence or absence of functional messenger RNA. Methods were developed and scaled down to be compatible with clinical‐size biopsies.

(2) Total muscle RNA was prepared and translated in a rabbit reticulocyte cell‐free system. Neosynthesized products were isolated by immunoaffinity microchromatography. Phosphorylase was compared with control enzymes neosynthesized and purified under the same conditions.

(3) No functional mRNA for phosphorylase could be detected in the muscles of the two patients. A decreased amount of messenger for phosphorylase, compared with the control enzymes, was found in the muscles of the two heterozygotes.

(4) Exploration of functional messenger RNA in clinical enzymopathies should be readily adaptable to a number of enzymatic diseases.
Genetic linkage between the loci for myotonic dystrophy and peptidase D
Authors: O'BRIEN T. , BALL S. , SARFARAZI M. , HARPER P. S. , ROBSON E. B.
Published: September 2007

In a linkage study between myotonic dystrophy and peptidase D it is evident from the lod score values that with high probability θ lies between 0 and 0.1. The data thus support a previous hint of linkage between peptidase D and the Lutheran and secretor loci, which were already known to be linked to myotonic dystrophy.
Molecular studies on galactose 1 phosphate uridylyl transferase from normal and mutant subjects. An immunological approach
Authors: BANROQUES J. , SCHAPIRA F. , GRÉ; C. , DREYFUS J.‐C.
Published: September 2007

The mutant forms of uridylyl transferase of eight galactosemic patients and two ‘Rennes’ variants were characterized with regard to the presence and level of immunoreactive protein, the apparent subunit molecular weight and the isoelectric point. Semi‐purified haemolysates were studied by various electrophoretic techniques, then proteins were electrophoretically transferred on to nitrocellulose filters. They were treated with specific anti‐transferase antibodies, and then with radioiodinated protein A, followed by autoradiography. We have found that: (1) in all cases, a cross‐reacting material was detectable, with a molecular subunit size of 46000, indistinguishable from that of controls. (2) a biochemical heterogeneity of the mutant enzyme was found: the amount of apparent immunologically reactive protein varied from 20 to 100% of that of controls; electrophoretic experiments performed on two ‘Rennes’ variants showed an increased negative charge.
Quantitative variations in polymorphic types of human red cell esterase D
Authors: NISHIGAKI I. , ITOH T. , OGASAWARA N.
Published: September 2007

Human red cell esterase D was analysed quantitatively in Japanese samples. Among the three esterase D phenotypes there was a significant difference in catalytic activity, with an approximate ratio of 7:5:3 for EsD 1, EsD 2‐1 and EsD 2. With a few inter‐type individuals, the distribution of their activity values was plotted in a tri‐modal curve. These results suggest that the esterase D system in human red cells is qualitatively and even quantitatively controlled by genes.
Mutagen hypersensitivity in Friedreich's ataxia
Authors: EVANS H. J. , VIJAYALAXMI  , PENTLAND B. , NEWTON M. S.
Published: September 2007

Cultured blood lymphocytes from nine patients with Friedreich's ataxia (FrA) and nine matched controls were exposed to a series of graded doses of mitomycin C and ethyl methane sulphonate and examined for the incidence of sister chromatid exchange (SCE). The spontaneous SCE levels did not differ between patients and controls, but the cells from each of the patients showed a significantly enhanced response to the induction of SCE by both mutagens – the patients' cells being up to 50 % more sensitive than controls. Cultures from five FrA patients and five controls were analysed to determine the spontaneous incidence of chromosomal aberrations and exposed to a graded series of X‐ray doses to measure their response to radiation‐induced chromosome damage. The spontaneous aberration incidence in controls did not differ from that found in other control series, but the background incidence of aberrations in cells from the FrA patients was significantly above control levels and appeared to reflect an enhanced response to diagnostic exposure to radionuclides. The FrA cells showed a significantly enhanced in vitro response to chromosome aberration induction by X‐rays, the net aberration yields being some 60 % greater than those in irradiated controls at doses up to 200 rads. It is concluded that FrA is yet another syndrome which shows hypersensitivity to the induction of chromosome damage by mutagens. Possible factors responsible for this hypersensitivity are discussed and comparisons drawn with ataxia telangiectasia, another autosomal recessive disease characterized by enhanced X‐ray sensitivity.
Huntington's Chorea in the Netherlands The problem of genetic heterogeneity
Authors: WENT L. N. , VLIS M. VEGTER‐VAN DER , BRUYN G. W. , VOLKERS W. S.
Published: September 2007

For 1100 patients with Huntington's Chorea in 102 families from The Netherlands the average age at death per family is presented. This average ranges from 72 to 38 years. An analysis of variance of the data is strongly indicative of genetic heterogeneity. For the patients with the relatively high age at death little or no difference is observed from the age at death of their non‐affected parents and non‐affected sibs. Eleven children who presented with the juvenile form of the disease had all inherited the abnormal gene from their father. These 11 children were found only in families with an average age at death below 57 years. Other factors that might possibly influence the variation of average age at death between families are discussed, but cannot explain the observed differences.
Gene order and gene distances in the HLA region studied by the haplotype method
Authors: OLAISEN B. , TEISBERG P. , JONASSEN R. , THORSBY E. , GEDDE‐DAHL T.
Published: September 2007

The present report describes a method to establish gene order and gene distances in chromosomal regions where several genes are located closely together. The method is applied to the study of the complement loci in the HLA complex on chromosome 6 in man.

The method is based on allelic association, i.e. alleles of closely linked loci are nonrandomly associated on haplotypes. A haplotype which yields information has a frequency higher than would be expected from the frequencies of each of its alleles. They occur, moreover, with a frequency which makes them the main source of the least frequent of the alleles in the combinations. Other haplotype combinations involving this allele (these alleles) are most likely the results of recombinational events involving a main haplotype. Such crossovers may therefore, on certain conditions, be used for gene mapping purposes. Some basic rules for the use of the method are given.

A total of 701 haplotypes involving the short arm of chromosome 6 have been studied. Typings have been performed with regard to HLA‐A, ‐B, ‐C, ‐D/‐DR, C4, C2 and Bf. The study confirms previous localization of the complement loci between HLA‐D and ‐B. The investigation suggests the order HLA‐D‐Bf‐C4‐C2‐HLA‐B. There is, moreover, slight evidence in favour of a localization of the C4A gene on the HLA‐B side of C4B. Given an HLA‐A‐HLA‐B distance of 0.8 cM, suggested relative distances are: HLA‐D‐Bf: 0.44 cM, Bf‐C4: 0.04 cM, C4‐C2:0.11 cM, and C2‐HLA‐B:0.12cM.
Evidence for linkage between the loci for transferrin and ceruloplasmin in man
Authors: WEITKAMP L. R.
Published: September 2007

Lod score analysis indicates probable linkage between the loci for transferrin and ceruloplasmin at a recombination frequency of approximately 10–15%. This human linkage relationship is homologous to one previously reported for cattle.
Relationships between early mortality and sex ratio: changes over the last century in Italy
Authors: ULIZZI L.
Published: September 2007

Italy, like other industrialized countries, experienced during the last century a dramatic change in socio‐economic conditions and in sanitation. In order to ascertain whether the improvement in living conditions has modified the relationships between the sex ratio at birth and selection by early mortality (stillbirth, mortality up to 1 month, mortality up to 1 year of life), the secular trends of the sex ratio in total births, in survivors up to 1 month and up to 1 year of age have been calculated for the Italian population over the last century. The results can be summarized as follows:

(i) the sex ratio in total births progressively decreases;

(ii) the sex ratio in survivors up to 1 year progressively increases.

As a result of these two opposite trends, the difference between sex ratio at birth and after the incidence of early mortality is progressively getting smaller.
Confirmation of the assignment of human biliverdin reductase to chromosome 7
Authors: Parkar M. , Jeremiah S. J. , Povey S. , Lee A. F. , Finlay F. O. , Goodfellow P. N. , Solomon E.
Published: September 2007

Segregation of biliverdin reductase (BLVR) in 11 independent human‐mouse hybrids confirms the assignment to chromosome 7 in man and gives a regional localization of 7pter → 7q22. Isoelectric focusing of BLVR reveals genetically determined variation among inbred strains of mice.
Surnames in Sardinia II. Computation of migration matrices from surname distributions in different periods
Authors: Wijsman E. , Zei G. , Moroni A. , Cavalli‐Sforza L. L.
Published: September 2007

A method is described for obtaining migration matrices from data on frequency distributions of transmissible traits in at least two different periods. In the present case, surname frequency distributions were used. In this way migration matrices describing rates of movement among nine areas of Sardinia were found for the period 1850–1970. Data were kinship matrices from surname distributions over two or three time periods. Population growth was included in the model under the assumption that expected family size in all areas was constant, or that outside estimates of the relative family sizes exist. Use of variable vs. constant growth rates did not drastically affect the estimated matrices.

The matrices estimated for different time periods are similar. Estimates of net migration into the different areas were relatively insensitive to different methods of summarizing statistics.

The elements of the matrices indicate strong effects on migration rates of distance between areas, and somewhat weaker effects of economic differences. The diagonal elements of the matrices show a high negative correlation with independent estimates of rates of immigration into the same areas.
Review
Authors: Stewart G.
Published: September 2007

Book reviews in this articles

Gnetics of Neurological and Psychiatric Disorders. Association for Research in Nervous and Mental Disease.
Family data on sixteen chromosome 1 loci
Authors: Robson E. B. , King J.
Published: September 2007

Lod scores are presented from the published and unpublished data of the Galton Laboratory, and from published data on sixteen chromosome 1 loci, AMY, AT3, CAE, CMT1, ELI, ENO1, FUCA, Fy, GDH, PEPC, PGD, PGMI, Rh, Sc, UMPK and 1qh.
Genetic aspects of erythropoietic protoporphyria
Authors: WENT L. N. , KLASEN E. C.
Published: September 2007

An exhaustive study of erythropoietic protoporphyria in the Netherlands led to the discovery of 200 patients with this disorder in 91 families. In 46 of these families a single patient occurred. A study of parents, sibs and children led to the conclusion that the disease of erythropoietic protoporphyria is inherited as an autosomal recessive disorder. The presence of an occasional fluorescent red blood cell combined with normal protoporphyrin levels was observed in half of the children and sibs of patients and one of their parents; this phenomenon is therefore inherited as an autosomal dominant character. From an analysis of the findings in the 91 families we put forward the hypothesis of a 3‐allele system.
Linkage of the LW blood group locus with the complement C3 and Lutheran blood group loci
Authors: SISTONEN P.
Published: September 2007

Segregation data on LW in families of informative males show that the LW (Landsteiner‐Wiener) blood group locus is closely linked to the complement C3 locus and to the locus for the Lutheran blood group. This finding also confirms the presence of a larger linkage group on chromosome 19, including now the loci for apoE, Le, C3, LW, Lu, Se, H, PEPD, myotonic dystrophy (DM), neurofibromatosis (NF) and familial hypercholesterolemia (FHC). Linkage of LW with the Lewis blood group locus could not be definitely established by the present family data, but small positive scores between LW and Le suggest that the Le locus is situated outside the C3‐LW region.
Regional localization of 3 Y‐derived sequences on the human X and Y chromosomes
Authors: WOLFE J. , ERICKSON R. P. , RIGBY P. W. J. , GOODFELLOW P. N.
Published: September 2007

The structure of the Y chromosome and the relationship between the human sex chromosomes have been studied using Y‐derived sequences cloned in cosmids. Two probes recognize different unique sequences which map to the heterochromatic part of the long arm of the Y chromosome. A third sequence is shared by the long arm of the X chromosome and the euchromatic part of the Y chromosome. Thus homology between the sex chromosomes occurs outside the pairing region.
Body size and shape in 46, XX males: an anthropometric investigation
Authors: VARRELA J.
Published: September 2007

Anthropometric measurements of four 46, XX males are compared with those of their first degree male relatives, control males, and a sample of 47, XXY males. Most dimensions of 46, XX males are smaller than those of normal males. 46, XX males are also shorter and smaller than 47, XXY males.

The present results support the earlier suggestion that there is a gene(s) in the Y chromosome with a general size‐increasing effect and that the Y chromosome has an active role in the development of sex dimorphism in many body dimensions. These four 46, XX males may possess the Y chromosomal gene which sets the later timing of development in males.
A general expression for the variance–covariance matrix of estimates of gene frequency: the effects of departures from Hardy–Weinberg equilibrium
Authors: MENDELL N. R. , SIMON G. A.
Published: September 2007

Error variances and covariances are derived for estimates of gene frequencies found by allele counting in cases where the Hardy–Weinberg law does not necessarily hold.
Genetic variants of human erythrocyte glucose‐6‐phosphate dehydrogenase: new characterization data obtained by multivariate analysis
Authors: VERGNES H. A. , BONNET L. G. , GROZDEA J. D.
Published: September 2007

Thirteen variables used in the course of characterization of G6PD variants from forty‐one individuals have been submitted to multivariate factorial and cluster analysis. Because of the diagrammatic representation of the analysis, two main findings were made possible. Firstly, the three‐dimensional plot of the experimental data gives the advantage of a model of classification which is closely related to the ethnogeographical origin of the subjects, and to the clinical and haematological incidence of the G6PD variants. Secondly, cluster analysis visualizes the distance between the G6PDs examined. In this respect, it was determined that three local original variants associated with acute haemolytic anaemia showed a close relationship and belonged to the same cluster (Gd(—) Toulouse, Gd(—) Muret and Gd(—) Colomiers). Conversely, two non‐haemolytic variants (G6PD Luz Saint Sauveur and Lozère) were found to be linked in another remote cluster. The procedure developed in this work promotes a new approach to G6PD characteristics in human genetic studies.
Twinning rates in Fiji
Authors: POLLARD R.
Published: September 2007

The incidence of twins in Fiji has been investigated using birth registrations for the years 1976–81. The twinning rate for the indigenous Fijians is found to be 9–4 per 1000 live maternities, (based on 407 sets of twins), and for Indians, descendants of immigrants who began to arrive in Fiji in 1879, 6·2 per 1000 (based on 350 twins). After standardizing for maternal age, the difference between the two ethnic groups decreases slightly, but the Fijian rate remains almost 40% above that of the Indians. This difference is consistent over the 6 years of the study, is found for mothers of all age groups under 40 and at all levels of parity. An analysis of hospital records in Fiji produces higher twinning rates for both Fijians and Indians, but a similar difference is found between the two ethnic groups. Although the twinning rate for Fijians is lower than that reported for other Melanesian people, it is well above reliable rates found for Mongoloid races from whom the Fijian is descended. The sparse information on twinning rates among Polynesians suggests rates not dissimilar from Melanesians, so that no support for the hypothesis of low twinning rates in the Pacific is evident. The twinning rate for Indians in Fiji is lower than rates reported from the Indian subcontinent.
The analysis of intraclass correlation in multiple samples
Authors: DONNER A.
Published: September 2007

A unified methodology is presented for the analysis of intraclass correlation in two or more samples, with emphasis on application to family studies. The methodology provides point and interval estimates of a common intraclass correlation in data having either fixed or variable class sizes. Tests of homogeneity for intraclass correlation coefficients are also discussed.
A population study of alpha‐keto acid reductase
Authors: FRIEDRICH C. A. , FERRELL R. E.
Published: September 2007

An electrophoretic survey of 509 individuals of Japanese, Mexican American, American Negro, Eskimo, Amerindian and Anglo‐American origin failed to reveal genetically determined variation at the alpha‐keto acid reductase locus by starch gel electrophoresis. Additional screening of 232 individuals by thin layer isoelectric focusing in polyacrylamide gels detected a single phenotype. Interspecific variation at the alpha‐keto acid reductase locus is clearly resolved using either method. These results indicate that the alpha‐keto acid reductase locus is monomorphic in most human population groups despite earlier results suggesting the existence of genetic polymorphism.
Localization of the human aryl hydrocarbon hydroxylase gene to the 2q31→2pter region of chromosome 2
Authors: OCRAFT K. P. , MUSKETT J. M. , BROWN S.
Published: September 2007

Analysis of hybrid cells containing fragments of human chromosome 2 has resulted in the regional localization of a gene for aryl hydrocarbon hydroxylase (AHH). Hybrids prepared from a human cell line containing an established translocation have shown that AHH can be localized to the region 2q31→2pter.
Isolation of a cDNA clone for the human muscle specific carbonic anhydrase, CAIII
Authors: LLOYD J. C. , ISENBERG H. , HOPKINSON D. A. , EDWARDS Y. H.
Published: September 2007

The molecular cloning of cDNA for the human muscle specific carbonic anhydrase CAIII is described. The recombinant was isolated from a human muscle cDNA library prepared in the expression vector Λgt11, and was characterized by hybridization selection and immunoprecipitation. A comparison of insert cDNA and mRNA sizes suggests that the cDNA is full length and includes extensive untranslated sequences. Preliminary sequence data have confirmed the authenticity of this clone and Southern blotting of human and rodent DNA indicates that it will be a useful probe in the analysis of somatic cell hybrids.