bluuebunny/crossref_metadata_2025 huggingface dataset:
Confirmation that the Type I collagen gene on chromosome 17 is COL1A1 (α1(I)), using a human genomic probe
Authors: Solomon E. , Hiorns L. , Sheer D. , Rowe D.
Published: September 2007

A cloned 15 kb genomic fragment from the human α1 (I) collagen gene (COL1A1) has been used as a probe on restriction digests of DNA from human‐mouse somatic cell hybrids. Positive results on hybrids containing chromosome 17 as their only karyotypically visible human material confirm the assignment of this gene to chromosome 17. Hybrids which contain fragments of chromosome 17 are used to confirm the localization to 17q21‐qter.
Advanced grandmaternal age on the mother's side – a risk of giving rise to trisomy 21
Authors: Aagesen L. , Grinsted J. , Mikkelsen M.
Published: September 2007

The age distribution of maternal grandmothers of children with Down syndrome was compared with paternal grandparents of the same group and with grandparents of healthy children (controls). The significant advanced maternal grandmaternal age was found in cases of Down syndrome caused by first meiotic error in the maternal oogenesis. The advanced maternal grandmaternal age was found independent of maternal age. No differences were found between the ages of grandfathers of Down syndrome and of controls.
Complete hydatidiform moles combine maternal mitochondria with a paternal nuclear genome
Authors: EDWARDS Y. H. , JEREMIAH S. J. , McMILLAN S. L. , POVEY S. , FISHER R. A. , LAWLER S. D.
Published: September 2007

The parental origin of mitochondria in hydatidiform moles has been investigated by analysis of genetic variants of mtDNA restriction enzyme patterns. In six complete moles the mtDNA was found to be maternal in origin, with no contribution from the sperm mitochondria, while the nuclear genome was shown to be exclusively paternal in five cases. The occurrence of mtDNA variation in the healthy population was investigated using white blood cells and placentae, and the most common variation occurred at the Ava II restriction sites. The variants exhibited by molar mtDNA were the same as those found in material from healthy individuals.
Biochemical heterozygosity as a predictor of developmental homeostasis in man
Authors: LIVSHITS G. , KOBYLIANSKY E.
Published: September 2007

The relationships between the variability of 48 morphological traits and the heterozygosity of four blood group loci were studied in 200 Israeli Jewish males of Eastern European origin aged 18–22 years. A definite correlation was observed between the level of heterozygosity and the variability of 17 traits and two indices. Of the latter traits only 10 were chosen for further analysis. Principal component analysis showed that seven of these traits were independent. For six of them, the frequency of modal individuals (average ± 0·67 s.d.) in the tetraheterozygous group was the highest, diminishing proportionally with decreasing heterozygosity levels. The degree of heterozygosity also had a significant negative correlation with the coefficient of variation of the morphological characters and was positively associated with the kurtosis values. Only the variability of one of 10 traits showed an opposite trend and a correlation with biochemical homozygosity. The results are discussed in terms of developmental homeostasis.
The estimation of inbreeding from isonymy: relationship to the average inbreeding coefficient
Authors: TAY J. S. H. , YIP W. C. L.
Published: September 2007

The inbreeding coefficient estimated by the isonymy method is often much larger than the average inbreeding coefficient (FD). One reason commonly stated is that the surnames are polyphyletic in origin in such cases. The purpose of this paper is to examine the relationship between the inbreeding calculated from isonymy and the average inbreeding coefficient. It was found that when the level of inbreeding is low, especially when the random isonymy (Pr) is much larger than FD, or when the number of surnames is small (which results in a larger value of Pr), isonymy tends to grossly overestimate FD. A small number of surnames per se (not necessarily due to polyphyletic origin of surnames) will be likely to result in an unduly high estimate of inbreeding. The equations established are illustrated by numerical examples.
Genetic heterogeneity of the B subunit of coagulation factor XIII: resolution of type 2
Authors: BOARD P. G.
Published: September 2007

An apparent discrepancy in phenotyping the genetic polymorphism at the FXIII B locus by electrophoresis or isoelectric focusing has been investigated. The data indicate that the product of the type 2 allele, which can be detected by agarose electrophoresis, is not resolved from the product of the type 1 allele by isoelectric focusing. The understanding of this problem has previously been confused by the absence or very low frequency of the type 2 allele in Japanese populations studied by isoelectric focusing and electrophoresis.

An alternative enzyme‐linked immunoblotting technique is described which substantially improves the method for phenotyping products of the FXIII B locus after electrophoresis.
A revised map of chromosome 1
Authors: SHERMAN S. L. , KING J. , ROBSON E. B. , YEE S.
Published: September 2007

The genetic map of chromosome 1 reported by Keats, Morton & Rao (1981) has been updated using recent recombination data and regional assignments from the Galton Laboratory (King, 1982a) and from the current literature. A maximum likelihood mapping technique using pairwise recombination data without a chiasma map was developed, based on the principles of Rao et al. (1979) and Keats et al. (1981). The development of this new method was found to be necessary when inconsistencies were encountered using a method which combines recombination data and physical data through the chiasma map. These inconsistencies could be due to appreciable chiasma movement, incorrect physical assignments or technical and biological variation in lod scores.
Approximate linkage equilibrium between two polymorphic sites within the gene for human complement component 3
Authors: DONALD J. A. , BALL S. P.
Published: September 2007

Haplotypes have been determined for alleles at two separate polymorphic sites within the human structural gene for complement component 3, identified as a protein polymorphism and as a restriction fragment length polymorphism by hybridization using a cloned gene probe. No evidence was found for appreciable disequilibrium between alleles at these sites, despite their very close linkage.
A direct cytogenetic technique for assessing the rate of first meiotic non‐disjunction in the human male by the analysis of cells at metaphase II
Authors: LAURIE D. A. , FIRKETT C. L. , HULTÉN M. A.
Published: September 2007

The successful application of a triple staining technique incorporating quinacrine mustard fluorescence, lacto‐propionic orcein staining and C‐banding to metaphase II cells in the human male is described. This procedure overcomes the major technical difficulties associated with the analysis of these cells, enables unambiguous chromosome counts to be made and allows the majority of cells to be karyotyped. Preliminary results on two hundred cells from six men with apparently normal karyotypes are presented.
Chiasma derived genetic lengths and recombination fractions: a 46, XY, t(9; 10) (p22; q24) reciprocal translocation
Authors: LAURIE D. A. , PALMER R. W. , HULTÉN M. A.
Published: September 2007

Chiasma distribution data on chromosomes 1, 2 and 9 from a reciprocal translocation carrier with a 46, XY, t(9; 10) (p22; q24) karyotype were used to calculate genetic distances and recombination fractions for chromosome segments corresponding to the major mitotic bands and for intervals between the centromeres and points at 10% intervals along the chromosome arms. These values were compared with those from control males with normal karyotypes. The translocation showed a marked increase in crossing‐over in one specific region of chromosome 9 and, in addition, there was evidence of interchromosomal effects in chromosomes 1 and 2.
The location of the major bands on chromosome 1 at diakinesis in the human male and the relationship between banding pattern and chiasma localization
Authors: LAURIE D. A. , HULTÉN M. A. , PALMER R. W.
Published: September 2007

Q‐banded chromosome 1 bivalents from six human males were measured in order to determine the locations of the major band borders. Chiasma position was also recorded in these bivalents in order to determine whether chiasmata preferentially occurred in Q‐bright regions, Q‐dark regions or in the interfaces between. The results indicated that the locations of the major bands of chromosome 1 were very similar at diakinesis and at mitotic prometaphase and that chiasma distribution was not governed by the banding pattern of the chromosome.
The affected sib method. IV. Sib trios
Authors: PAYAMI H. , THOMSON G. , MOTRO U. , LOUIS E. J. , HUDES E.
Published: September 2007

The classical sib pair method uses the expected and observed HLA (human leukocyte antigen) haplotype sharing distribution in sib pairs, who are affected with an HLA associated disease, to make inferences about the inheritance of the disease. In this paper we present the expected HLA haplotype sharing distributions in affected sib trios, and sib pairs, from families with three or more affected sibs. The underlying model for both distributions, as for the classical sib pair method, is that disease predisposition is determined by a single allele at an HLA‐linked locus. The sib trio tests of hypotheses (additive and recessive), and disease parameter estimates (additive, recessive and intermediate), can be compared with those obtained from the classical sib pair analysis. In addition, the sib trio data allow parameter estimation for a general disease model to be made, if the data fall within the bounds of the expectation. This study forms the basis of later investigations which show that haplotype sharing of affected sib trios for two susceptibility alleles (negative complementation) model, which appears appropriate for insulin dependent diabetes mellitus (IDDM), moves outside the bound of the single susceptibility expectations outlined here, whereas haplotype sharing values for sib pairs are bound by the single susceptibility allele expectations. Available Caucasian IDDM data have been analysed. The results support genetic heterogeneity of IDDM.
Chromosomal assignment of seven human genomic DNA sequences associated with restriction fragment length polymorphisms
Authors: SPURR N. K. , FEDER J. , BODMER W. F. , GOODFELLOW P. N. , SOLOMON E. , CAVALLI‐SRORZA L. L.
Published: September 2007

Seven phage clones containing human sequeces were picked at random from at human genomic library cloned in Charon 4A. The clones are devoid of repetitive sequences and can be used to recognize restriction fragment length polymorphisms (Feder et al. 1985. The chromosomal locations of the sequences defined by the seven clones have been determined by Southern blotting and DNA hybridization to DNA from human‐mouse somatic cell hybrids. The chromosomal assignment of these sequence should increase their value as genetic markers in family studies.
Different break‐points in Philadelphia chromosome variant translocation and in constitutional and sporadic translocations
Authors: MASERATI E. , PASQUALI F. , PERETTI D.
Published: September 2007

Three different samples of translocations were considered in an attempt to identify those chromosomal bands preferentially involved in variant Philadelphia chromosome (PH1) translocations, and to compare them with bands preferentially broken in constitutional and sporadic translocations. The first sample included 204 cases of variant Ph1 translocations with 221 identified break‐points (bp), the second consisted of 106 cases of non‐Robertsonian constitutional translocations with 213 bp identified, and the third one of 185 bp identified in sporadic translocations found occasionally in single cells of subjects with normal karyotypes and without haematological disorders.

A statistical analysis demonstrated that there are some bands preferentially broken in each of the samples, and this with a high level of significance (p < 0.001). The analysis of the distributions of the χ2 components permitted us to identify the 12 bands preferentially involved in variant Ph1 translocations and the 13 and 9 bands preferentially involved in constitutional and sporadic translocations, respectively. The comparison among the groups of preferential bp showed that the bands most involved in the three samples are different.

Some theoretical problems related to the origin of the Ph1 chromosome are discussed.
Assignment of the human gene for uridine 5‘‐monophosphate phosphohydrolase (UMPH2) to the long arm of chromosome 17
Authors: WILSON D. E. , SWALLOllW D. M. , POVEY S.
Published: September 2007

Two distinct isozymes of uridine 5′‐monophosphate phosphohydrolase (UMPH) have been identified in mammalian cells. Both of these isozymes hydrolyse other pyrimidine nucleotides. One of the isozymes, UMPH2, is more active against deoxy‐nucleotides than non‐deoxynucleotides and has a wider substrate specificity. We examined the segregation of the human gene for UMPH2 in human‐mouse somatic cell hybrids. Electrophoretic analysis of UMPH2 in hybrids suggested that the enzyme is a dimer. Human UMPH2 cosegregated with the long arm of chromosome 17 in the nineteen hybrids examined. The ease of separation of the rodent and human isozymes of UMPH2 and the relative simplicity of the enzyme assay suggest that UMPH2 may be a more useful marker gene for chromosome 17 than galactokinase.
Clinical and genetic studies in six Dutch kindreds with the Dysplastic Naevus Syndrome
Authors: BERGMAN W. , PALAN A. , WENT L. N.
Published: September 2007

In an ancient fishing village in the neighbourhood of Leiden a cluster of melanoma‐prone families was detected. In these families atypical precursor naevi were recognizable in many melanoma patients and in their relatives. This combination of symptoms is called the Dysplastic Naevus Syndrome (DNS). The spectrum of clinical signs characterizing the phenotype of the DNS ranged from apparent lack of gene‐expression through minimal to obvious manifestations.

Genetic analysis of six pedigrees revealed an autosomal dominant mode of inheritance, with a very variable expressivity of the gene, which is also rather frequently non‐penetrant. The total number of family members (affected or at risk) was 314, 243 of which were alive and were personally examined by us. In the six pedigrees a total of 33 patients with melanoma occurred.

In thirty patients with multiple atypical naevi, the clinical diagnosis of DNS was histologically verified. A further thirty‐six patients with several atypical naevi were also regarded as gene carriers.

Fifteen ‘normal ’ individuals had to be gene‐carriers on the basis of their position in the pedigree.
Inherited electrophoretic variants detected in a Japanese population with two‐dimensional gels of erythrocyte lysates
Authors: TAKAHASHI N. , NEEL J. V. , NAGAHATA‐SHIMOICHI Y. , ASAKAWA J. , TANAKA Y. , SATOH C.
Published: September 2007

Genetic variation has been studied in erythrocyte lysates from 100 Japanese children and their parents by means of two‐dimensional polyacrylamide gel electrophoresis. Fifty‐five polypeptides selected without respect to variability were considered suitable for scoring. Genetic variation was encountered in 14 of these polypeptides. Family data show that the segregation of 13 variants is consistent with an autosomal codominant mode of inheritance; the remaining variant exhibits a sex‐linked mode of inheritance. Of 8 presumably identical polypeptides found variable in Japanese and/or Caucasians, differences in the occurrence or allele frequencies of polymorphisms were recognized for four. Contrary to the experience of some investigators, the amount of variation and the ethnic differences we are encountering indicate that two‐dimensional polyacrylamide gel electrophoresis is a sensitive tool for the study of genetic events.
The 12E7 red cell quantitative polymorphism: control by the Y‐borne locus, Yg
Authors: TIPPETT P. , SHAW M.‐A. , GREEN C. A. , DANIELS G. L.
Published: September 2007

Family and sibship analyses prove that the 12E7 quantitative polymorphism of red cells is controlled by a Y‐borne locus, Yg, in addition to the X‐borne locus, Xg. X‐Y recombination is invoked to explain the apparent exception to Y‐borne control of the 12E7 polymorphism in one family.
Genetics of Hunter Syndrome: carrier detection, new mutations, segregation and linkage analysis
Authors: CHASE D. S. , MORRIS A. H. , BALLABIO A. , PEPPER S. , GIANNELLI F. , ADINOLFI M.
Published: September 2007

We have investigated 31 families segregating for Hunter Syndrome in order to advance our understanding of the genetics of this disease. The hair root test for the diagnosis of carriers of Hunter Syndrome was improved by the adoption of a new diagnostic index that distinguishes between carrier and normal females better than previous methods of analysis. One hundred and eleven female relatives of the affected children were tested by such procedures. This showed that seven out of 31 mothers were not carriers (22.6%), thus suggesting a small deficit of new mutations relative to the expectation that 33 % of lethal, recessive alleles arise anew in a population at equilibrium at a sex‐linked locus with equal mutation rates in male and female gametogenesis. The difference, however, is not statistically significant. The age of the parents of new mutants was slightly but significantly raised. Nevertheless, the independent increase in the age of the fathers of new female mutants was not statistically significant. Finally, a deficit of affected males was observed. This was significant and suggests the possibility of intrauterine loss of some affected males.

Linkage analysis between the Hunter Syndrome locus, three polymorphisms in the Factor IX gene and the anonymous polymorphic probes 52A and DX13 showed that the Hunter locus is fairly closely linked to DX13, and hence distal to the Factor IX gene, while no linkage was observed with the 52A polymorphic site.

The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at θ= 025; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at θ= 01.
Dermatoglyphic findings in fragile X syndrome: a causal hypothesis points to X‐Y interchange
Authors: LOESCH D. Z.
Published: September 2007

Dermatoglyphic analysis which included topological pattern elements, pattern intensities and dermatoglyphic measurements was performed in 90 male and 110 female fragile X subjects. Data on cytogenetic and intellectual assessments were also available in these individuals. The following conclusions have been drawn from the obtained results.

1. The fragile X syndrome is associated with an appreciable deviation in dermatoglyphic patterns and measurements, especially in males, which may be utilized for diagnostic purposes.

2. The variability in patterns and measurements is considerably increased which, together with irregular distributions, indicates that the fragile X condition may not be homogeneous.

3. The type of deviation in either sex is not inconsistent with the effect of an excessive dosage of the Y, combined with a deficit of the X chromosome and is, therefore, indicative of the X‐Y chromosomal rearrangement as an initial lesion in fragile X. Since the deviation may not be specific, direct evidence for such rearrangement should be sought by means of molecular techniques.
Genetic heterogeneity of S‐formylglutathione hydrolase
Authors: BOARD P. G. , COGGAN M.
Published: September 2007

S‐formylglutathione hydrolase from erythrocytes has been studied by an electrophoretic technique. Three phenotypes were observed in a number of racial groups. The electrophoretic polymorphism was shown to be the product of two alleles at a single locus termed FGH. The product of the type 2 allele was found to be relatively unstable.
Characterization and use of somatic cell hybrids with interspecific translocations involving the human X chromosome
Authors: BOYD Y.
Published: September 2007

Two hybrid cell lines, whose only human material was a portion of the X translocated on to a mouse chromosome, have been characterized by cytogenetics, in situ hybridization and Southern blotting. In one hybrid (HORL911R8B) the region Xpter to Xq2(2–4) was identified. In the other (PIP) the single human fragment was found to contain sequences from two separate X chromosomal regions (corresponding approximately to Xp11.4–Xp22.1 and Xq26–Xqter). These two hybrids in combination with a third (WAG 8) retaining Xqter to Xp21 as a human X‐autosome translocation chromosome, form a mapping panel for rapid subregional assignments to the human X chromosome. This mapping panel has been used to provide information about the order of DNA sequences derived from the X chromosome and to provide an assignment for an anonymous DNA segment, M201γ, to Xp11.4–Xp21.1.
The effect of recombination between the X and Y chromosomes of mammals
Authors: BENGTSSON B. O. , GOODFELLOW P. N.
Published: September 2007

Recent molecular analysis has proved the hypothesis that parts of the human sex chromosomes are homologous and can recombine in male meiosis. The biological consequences of this recombination have been investigated by considering the joint effect of neutral mutation and random genetic drift on a locus that is closely linked to the non‐homologous segments of the sex chromosomes, but which recombines with them in an appreciable frequency. Our model predicts that, in the absence of selection, allelic differentiation between genes carried on the X and on the Y chromosomes will develop only if the recombination rate is of the same order of magnitude as the mutation rate or smaller.

Similarly, a mutation favourable in males but disadvantageous in females will increase in frequency on the Y chromosomes, while remaining rare on the X chromosomes, only if the recombination rate is smaller than the fitness advantage of the mutation.

The X and Y chromosomes are, thus, not expected to show any genetic differentiation for almost all of their homologous parts. Divergence will occur only for loci that very rarely recombine between the sex chromosomes.
Localization of PEPD to the long arm of chromosome 19
Authors: DAVIS M. B. , SCHONK D. , MONTEIRO M. , OERLEMANS F. , POVEY S. , WIERINGA B.
Published: September 2007

A panel of human‐rodent somatic cell hybrids containing different regions of chromosome 19 has been used to obtain a regional localization for peptidase D. The results assign PEPD to the long arm of chromosome 19, in the region cen‐g13.2.
Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations
Authors: FALK C. T. , RUBINSTEIN P.
Published: September 2007

An alternative to Woolf's (1955) relative risk (RR) statistic is proposed for use in calculating the risk of disease in the presence of particular antigens or phenotypes. This alternative uses, as the control sample, the parental antigens or haplotypes not present in the affected child. The formulation of a haplotype relative risk (HRR) thus eliminates the problems of sampling from the same homogeneous population to form both the disease sample and an appropriate control.

We show that, in families selected through a single affected individual, where transmission of the four parental haplotypes can be followed unambiguously, the mathematical expectation of the HRR is identical to that of the RR. Since the sample formed from the ‘non‐affected’ parental haplotypes is clearly from the same population as the disease sample, the HRR thus provides a reliable alternative to the RR. A further advantage obtains when family data are being collected as part of a study since the control sample is then automatically contained in the family material.

Data from studies of patients with insulin dependent diabetes mellitus (IDDM) are used to obtain an estimate of the risk to those with HLA antigens or phenotypes associated with IDDM using the HRR statistic. A comparison of the HRR's and RR's for these data is also presented.
Antigen sharing in couples in a two‐locus ABO‐like system
Authors: LARSEN S. O. , HANSEN H. E.
Published: September 2007

The probabilities with which the two members of a couple share no, one or two antigens on each of two loci in ABO‐like systems are derived. As an example, expected values concerning the HLA‐A, B system are compared with observed frequencies in a material of 690 couples. A FORTRAN program for calculation of the gene‐sharing probabilities is available.
Breakpoint distribution in constitutional chromosome rearrangements with respect to fragile sites
Authors: PORFIRIO B. , DALLAPICCOLA B. , TERRENATO L.
Published: September 2007

In an attempt to investigate possible relationships between fragile site bands and chromosome abnormalities, we have analysed the distribution of 6391 breakpoints found in constitutional rearrangements.

Were relative band lengths to be ignored, a general trend for breaks to be located in fragile site bands would be confirmed. On the other hand, no difference was detected between bands with or without fragile sites if the probability of breakage for each single band is assumed to be proportional to its length. Nevertheless, a number of bands with a great excess of breakage events were identified.
Biochemical and genetic identity of alpha‐keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes
Authors: FRIEDRICH C. A. , FERRELL R. E. , SICILIANO M. J. , KITTO G. B.
Published: September 2007

We have recently shown that cytoplasmic malate dehydrogenase (MDH‐s) from several non‐human species catalyses the reduction of aromatic alpha‐keto acids in the presence of NADH (Friedrich et al. 1987), an activity previously attributed to the enzyme aromatic alpha‐keto acid reductase (KAR E.C. 1.1.1. 96). Here we present evidence that this also occurs in humans, and that the previously characterized human KAR is not the product of a genetically distinct locus.

Human MDH‐s and KAR activities co‐migrate after starch gel electrophoresis, and electrophoretic variants of human MDH‐s exhibited identical variation for KAR. Both enzymes show almost no electrophoretic variation among human populations of diverse origin. The reduction of aromatic alpha‐keto acids is substantially inhibited by malate, the end‐product of the MDH reaction. Antibodies raised against purified chicken MDH‐s equally inhibited both MDH‐s and KAR in chickens and humans. The bulk of the KAR activity in human blood appears to be due to MDH‐s, with a minor fraction catalysed by LDH, as is the case in most other species studied.

The previous assignment of a gene for KAR to human chromosome 12 in human/Chinese hamster somatic cell hybrids is questioned because interspecific hybrid bands of both MDH‐s and LDH appear with slightly different mobility approximately midway between the human and hamster controls in somatic cell hybrid studies, and the meaning of this artifact is discussed.

The discovery that MDH reacts with intermediate metabolites of phenylalanine and tyrosine has implications in relation to the mechanism by which mental retardation may be produced in phenylketonuria (PKU), and the effect of MDH inhibition on oxidàtive phosphorylation in the various tyrosinaemias is discussed.
A new method to test genetic models in HLA associated diseases: the MASC method
Authors: CLERGET‐DARPOUX F. , BABRON M. C. , PRUM B. , LATHROP G. M. , DESCHAMPS I. , HORS J.
Published: September 2007

We propose a new method to analyse data on HLA associated diseases. The method uses the simultaneous information on the marker associations and segregation with the disease. It may also take into account the differential risk of being affected for specific relatives of a patient as well as the differential HLA haplotype sharing according to the marker genotype of the patient. It is based on the principle of minimization of a sum of independent chi‐squares. It allows us to test the goodness‐of‐fit of various models in an easy and economical way.

The method is applied to a sample of 269 French IDDM patients and their relatives leading to the rejection of models with one locus closely linked to HLA with two and three alleles.
Mitochondrial DNA polymorphisms in Italy; III. Population data from Sicily: a possible quantitation of maternal African ancestry
Authors: SEMINO O. , TORRONI A. , SCOZZARI R. , BREGA A. , BENEDICTIS G. De , BENERECETTI A. S. SANTACHIARA
Published: September 2007

mtDNA polymorphisms were studied in a sample of 90 individuals of the Sicilian population using six restriction enzymes: HpaI, BamHI, HaeII, MspI, AvaII and HincII.

(1) Three new patterns, for MspI, AvaII and HincII, have been detected.

(2) At least two different mutations were found to account for both the AvaII morph 3 and the AvaII morph 9 as in many other Caucasian groups so far examined.

(3) Seventeen types were found; of these six are new.

The frequency (54.5%) of type 1–2 (2.1.1.1.1.2) is lower than in the rest of Italy whereas those of type 6‐2 (2.1.2.1.1.2) (10.0%) and type 18‐2 (2.3.1.4.9*.2) (12.2%) lie at the upper level of the Italian range.

The 18‐derivative, type 57‐2 (2.3.1.4.13*.2), which is consistently found in all Italian samples, is present also among Sicilians with an incidence of 2.2%.

(4) Of particular interest is that the HpaI‐3/AvaII‐3 complex, which is unique to groups of African ancestry, was found in Sicily at a frequency of 4.4%. For the first time an estimate of the amount of gene flow from Blacks to the Sicilian gene pool could be obtained.
Review
Authors: EDWARDS J. H.
Published: September 2007

Book reviewed in this article:

Molecular Evolutionary Genetics. By M. NEI.
The assignment of the genes coding for human complement components C6 and C7 to chromosome 5
Authors: JEREMIAH S. J. , ABBOTT C. M. , MURAD Z. , POVEY S. , THOMAS H. J. , SOLOMON E. , DiSCIPIO R. G. , FEY G. H.
Published: September 2007

A panel of 19 somatic cell hybrids was tested for the presence of human sequences coding for complement components C6 and C7 by restriction enzyme digestion and Southern blots probed with human C6 and C7 cDNA probes. C7 was also detected by amplifying part of the human gene in hybrid DNA using the polymerase chain reaction. Detection of human C6 and C7 was completely correlated with the presence of chromosome 5.
Use of DNA amplification (PCR) and direct DNA sequencing in the characterization of C4 alleles
Authors: BERG E. S. , MARKUSSEN G. , TEISBERG P. , OLAISEN B.
Published: September 2007

A procedure for detailed characterization of individual C4 alleles has been developed. DNA containing the two polymorphic clusters of C4 was amplified in the polymerase chain reaction (PCR). Direct DNA sequencing of amplified DNA was then performed by a modification of previously described techniques. The results were confirmed by M13 sequencing.

Single C4A3 and C4B1 allele sequences were in accordance with previous reports. An individual typed C4A3B1 revealed double bands in the autoradiogram in the positions corresponding to the polymorphic nucleotides. We did not find the reported thymine in position 3641 specific for the C4A4 allele in an individual typed C4A4B2.
On the use of x2 tests for nested categorized data
Authors: PRUM B. , GUILLOUD‐BATAILLE M. , CLERGET‐DARPOUX F.
Published: September 2007

The use of the ordinary %2 test in the MASC method of comparing various genetic models is rigorously justified.
Counting algorithms for linkage: correction to Morton and Collins
Authors: LANDER E. S. , GREEN P.
Published: September 2007

In a recent paper, Morton & Collins (1990) claimed: (1) that the Lander‐Green algorithm for genetic linkage analysis is not the EM algorithm for finding the maximum likelihood map; and (2) that a proposed alternative algorithm does have these properties. Here, we show that these assertions are both incorrect: the Lander‐Green algorithm is an EM algorithm, while the Morton‐Collins algorithm is not. We note that Morton and Collins concur with these conclusions.
Multiple recombination events are responsible for the heterogeneity of α+‐thalassemia haplotypes among the forest tribes of Andhra Pradesh, India
Authors: FODDE R. , HARTEVELD C. L. , LOSEKOOT M. , GIORDANO P. C. , KHAN P. MEERA , NAYUDU N. V. S. , BERNINI L. F.
Published: September 2007

SUMMAKY

The presence of several polymorphic markers along the α‐globin gene complex allows the identification of haplotypes associated with a‐thalassemia determinants. These are found at very high frequencies in geographic areas where malaria is or has been endemic which suggests a positive selective role by the parasitic disease in favour of α+‐thalassemia mutants. A population survey among forest tribal communities from Andhra Pradesh, India, revealed the prevalence and molecular heterogeneity of α+‐thalassemia determinants presumably due to a long backdated malaria endemicity among these populations. Analysis of the tribal α‐thalassemia haplotypes has shown a great degree of genetic heterogeneity which can be explained as the result of multiple recombination events in the presence of natural selection by malaria.
A genetic reconstruction of the history of the population of the Iberian Peninsula
Authors: BERTRANPETIT J. , CAVALLI‐SFORZA L. L.
Published: September 2007

The genetic patterns detectable in human populations of the Iberian Peninsula are shown by means of ‘synthetic genetic maps’, i.e. geographic maps of the highest principal components (PC) of gene frequencies. This method of analysis separates independent patterns of the genetic landscape, which hopefully represents different, major evolutionary events of the past. Among these are clines established by ancient important migrations, and local differentiations of populations due to barriers responsible for relative isolation. Only events of some magnitude from a demographic point of view, involving populations having initially definite genetic differences are detectable by the method. For this to be true, the genetic consequences of these events must not have been entirely smoothed out by later, prolonged genetic exchange between neighbours; but simulations have shown that long clines produced by major migrations can be rather stable in time.

The first synthetic map, corresponding to the first PC, shows that the major difference in the Iberian Peninsula is that between people originally of Basque and non‐Basque descent. The recession in time of the boundaries of the Basque‐speaking area seems correlated with the progressive genetic dilution of the Basque genotype in modern populations, as we move away from the centre of the Basque area. Clearly there must have been a close relationship in the progressive loss of the Basque language and increasing genetic admixture with neighbours. Most probably, Basques represent descendants of Paleolithic and/or Mesolithic populations and non‐Basques later arrivals, beginning with the Neolithic.

The second synthetic map is correlated with early Neolithic infiltrations from the eastern edge of the Pyrenees. It has been shown by archaeologists that, in some areas, early Neolithics lived side by side at overlapping dates with well developed Mesolithics. The demographic impact of Neolithic farmers versus Mesolithics, and therefore their genetic influence was thus less important in the Iberian Peninsula than in Central Europe.

The third synthetic map shows a correlation with the linguistic and historical duality between the Atlantic and the Mediterranean fringes, which developed in the first millennium B.C. and was probably determined, to some extent, by infiltrations through the Pyrenees of the Urnfield cultural elements as well as by several other later events.
Genetic epidemiology of breast cancer in Britain
Authors: ISELIUS L. , SLACK J. , LITTLER M. , MORTON N. E.
Published: September 2007

A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0‐003 giving a lifetime penetrance of 0‐83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non‐significantly younger than isolated probands.
Polymerase chain reactions with alphoid‐repeat primers in combination with Alu or LINEs primers, generate chromosome‐specific DNA fragments
Authors: ERICKSON R. P. , GLOVER T. W. , HALL B. K. , WITT M.
Published: September 2007

Y alphoid primers in combination with Alu and LINEs primers generated new DNA fragments in polymerase chain reactions (PCR) on DNA from a Y‐only somatic cell hybrid but not from X‐only, 3‐only, or 21‐only hybrids. X alphoid primers used in a similar manner generated new DNA fragments from the X‐only hybrid, and 1 of the primers (X2) also generated new DNA fragments on 3‐only and 21‐only hybrids when used in conjunction with Alu or LINEs primers. In all but one case, consensus alphoid primers generated new chromosome‐specific fragments in PCR reactions with the Alu or LINEs primers. A search for cryptic Alu‐ or alphoid‐alone PCR products as the source for one Alu‐alphoid band (chosen at random) was negative. Partial sequencing of products demonstrated that alphoid and Alu sequences were indeed contiguous in some newly synthesized DNA fragments. While Alu or LINEs primers generate smears of DNA fragments on total human DNA, the alphoid‐nonalphoid repeat combinations generated electrophoretically distinguishable bands of DNA when the template was total DNA. While these were distinguishable with different chromosome‐specific alphoid primers, the DNA fragments were not of the same sizes as those generated with the chromosome‐only hybrids.
Comparison of asymptotic tests of the Hardy‐Weinberg distribution
Authors: Ginsburg E. Kh. , Axenovich T. I. , Babenko V. N.
Published: September 2007

Nine asymptotic tests of the Hardy‐Weinberg distribution have been analysed. It is shown that the usual x2 test is the most appropriate one, considering type I and I1 errors.
Dominant genes for colorectal cancer are not rare
Authors: HOULSTON R. S. , COLLINS A. , SLACK J. , MORTON N. E.
Published: September 2007

The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0·006 with a lifetime penetrance of 0·63. These genes account for 81% of colorectal cancer in patients under 35, however, by 65 about 85% are phenocopies.
Natural selection associated with birth weight. VI. Towards the end of the stabilizing component
Authors: ULIZZI L. , TERRENATO L.
Published: September 2007

The secular trend for stabilizing selection on birth weight has been analysed in Italy from 1954 to 1985 in order to study changes in the forces of natural selection which have occurred as a consequence of progress in health care. In previous papers we demonstrated a very rapid relaxation of stabilizing selection on birth weight. In this paper we show that in the last few years this kind of selection has been coming to an end for the vast majority of Italian newborns.
The effect of mutation on linkage disequilibrium
Authors: CAROTHERS A. D. , WRIGHT A. F.
Published: September 2007

The standard formula for the approach to linkage equilibrium between two diallelic loci, initially at disequilibrium, is expressed in terms of their probability of recombination (Li, 1955). By a simple extension, we show how to incorporate the effects of mutation at one or both loci. It can thereby be inferred that in general these effects are unlikely to be of major importance, contrary to some recent suggestions.
Regional localization of the intestinal mucin gene MUC3 to chromosome 7q22
Authors: FOX M. F. , LAHBIB F. , PRATT W. , ATTWOOD J. , GUM J. , KIM Y. , SWALLOW D. M.
Published: September 2007

The gene MUC3 which codes for a mucin expressed in intestine (Gum et al. 1990) has previously been mapped, using somatic cell hybrids, to chromosome 7. We describe here the regional localization of MUC3 to chromosome 7q22 by in situ hybridization. Preliminary linkage analysis using CEPH (Centre d'Étude du Polymorphisme Humain) families supports this assignment and places MUC3 in the same linkage group as COL1A2 and CFTR.
Disequilibrium of multiple DNA markers on the human Y chromosome
Authors: PERSICHETTP F. , BLASI P. , HAMMER M. , MALASPINA P. , JODICE C. , TERRENATO L. , NOVELLETTO A.
Published: September 2007

We characterized four DNA polymorphisms on the Y chromosomes of 123 males from five Caucasian populations. Three markers on the male specific portion of the chromosome varied appreciably in frequency among the populations. When combined, these markers define a limited number of haplotypes compared with the maximum expected on the basis of random association. The associations found in the five groups are qualitatively similar and are thus considered to be relatively stable on an evolutionary time‐scale and possibly to predate the divergence of Caucasian populations. However, the haplotype frequencies varied markedly among populations, even between weakly isolated areas such as northern vs. southern Sardinia. This may indicate rapid progression towards fixation of alternative types of Y chromosomes.

We also report data suggesting that the same associations no longer hold when examining a marker as close as 275 bp from the boundary of the pseudoautosomal region on the Y chromosome.
Testing the Hardy‐Weinberg law across strata
Authors: OLSON J. M.
Published: September 2007

The problem of testing the Hardy‐Weinberg law when data are sampled from several populations with different allele frequencies is considered. An Odds‐ratio representation of disequilibrium is proposed. This ration is assumed to be constant across strata, an assumption that seems more reasonalbe than that of previous authors of a constant difference in true and expected (undre equilibrium) heterozygote proportions. A score‐type test which optimally combines information from the separate strata is then drived using the theory of unbiased estimating equations. Simulations show that the new test has greater power than previously proposed tests when the disequilibrium ratio is constant across strata. The method is applied to glyoxable genotype data form populations in India.
Regional localization of the gene coding for the GM2 activator protein (GME2A) to chromosome 5q32‐33 and confirmation of the assignment of GM3AP to chromosome 3
Authors: SWALLOW D.M. , ISLAM I , FOX M. R. , POVERY S. , KLIMA H. , SCHEPERS U. , SANDHOFF K.
Published: September 2007

The gene coding for the GM2 activator protein (GM2A) was previously mapped by us to chromosome 5 by an ELISA‐based technique. Here we confirm this assignment using a PCR analysis of somatic cell hybrids and descrive a regional localization to chromosome 5q32‐33 by in situ hybridization. We also confirm the assignment of pseudogene GM2AP to chromosome 3.
Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34
Authors: JONES K. A. , FITZGIBBON J. , WOODWARD K. J. , GOUDIE D. , FERGUSON‐SMITH M. A. , POVEY S. , WOLFE J. , SOLOMON E.
Published: September 2007

The retinoid X receptor α is one of a number of retinoic acid receptors which are members of the steroid/thyroid hormone superfamily. Localization of RXRA was achieved using the polymerase chain reaction on a panel of somatic cell hybrids. A cosmid clone was isolated using the RXRA PCR product, and this was used to further localize the gene by fluorescence in situ hybridization to chromosome 9q34 distal to the dopamine β hydroxylase gene (DBH). This mapping position was confirmed by PCR on a panel of translocation hybrids.
Another procedure for the preliminary ordering of loci based on two point lod scores
Authors: CURTIS D.
Published: September 2007

Because of the difficulty of performing full likelihood analysis over multiple loci and the large numbers of possible orders, a number of methods have been proposed for quickly evaluating orders and, to a lesser extent, for generating good orders. A new method is proposed which uses a function which is moderately laborious to compute, the sum of lod scores between all pairs of loci. This function can be smoothly minimized by initially allowing the loci to be placed anywhere in space, and only subsequently constraining them to lie along a one‐dimensional map. Application of this approach to sample data suggests that it has promise and might usefully be combined with other methods when loci need to be ordered.
Disease susceptibility genes and the sib‐pair method: a review of recent methodology
Authors: SHAH S. , GREEN J. R.
Published: September 2007

There is now a considerable body of literature which describes and analyses various methods of testing for the presence of disease susceptibility genes by examining the degree of HLA haplotype sharing of parental haplotypes over random expectations amongst affected siblings. We here survey a number of improvements, generalizations and extensions of the earlier reported methods with the aim of bringing them to the attention of those who are collecting HLA or other haplotype data on familial disease.
Genomic cloning and localization by FISH and linkage analysis of the human gene encoding the primary subunit NMDAR1 (GRIN1) of the NMDA receptor channel
Authors: BRETT P. M. , BOURDELLES B. Le , SEE C. G. , WHITING P. J. , ATTWOOD J. , WOODWARD K. , ROBERTSON M. M. , KALSI G. , POVEY S. , GURLING H. M. D.
Published: September 2007

A cDNA clone of the NMDAR1 (isoform E) has been used to screen both lambda and eosmid genomic libraries. A genomic phage clone was identified and sequenced and was found to contain some of the 3′ coding regions of the GRIN1 gene. This clone was used to localize the gene using fluorescent in situ hybridization (FISH) to normal chromosomes, and also to a lymphoblastoid cell line containing a translocation involving chromosomes 9 and 15. FISH localized the gene to chromosome 9q34.3. The clone was used to screen a panel of genomic DNAs cut with 20 restriction enzymes. A VNTR sequence 5′ to the gene, which was polymorphic for a number of restriction enzymes, was detected. A PvuII fragment of the genomic clone was found to detect the VNTR on Southern hybridization. The polymorphic VNTR marker was mapped against chromosome 9q34 markers using linkage analysis in the CEPH families. The GRIN1 gene was linked to D9S7 with a maximum lod score of 20·09 at zero recombination fraction in males and 0·03 % recombination in females.