Crossover in a Spanish cystic fibrosis family

Summary We report a crossover between the Met and KM19 probes in a phenotypically normal sib from a Spanish cystic fibrosis family.     

Frequency of the ESD*5 allele in a Spanish population

The red blood cell esterase D (ESD) polymorphism was studied by means of IEF in a North-East Spanish population (Barcelona). Gene frequencies in 430 unrelated individuals were ESD*1: 0.888, ESD*2: 0.091 and ESD*5: 0.021. Our data confirm previous results showing that ESD*5 occurs in polymorphic frequency and has a Caucasian origin.     

Identification and functional perspective of a novel HLA-A allele: A*0279

A novel HLA-A allele, HLA-A*0279, was identified using PCR-SSP and PCR-SBT methods. It is inheritable. HLA-A*0279 differs from HLA-A*020601 by a single nucleotide at position 497 in exon 3, leading to an amino acid change from Threonine to Isoleucine at the alpha2 helix of HLA molecule. To investigate whether the altered amino acid residue could affect its peptide-binding repertoire, we compared the predicted crystal structure of HLA-A*020601 and HLA-A*0279 by Swiss-PdbViewer software analysis. We found that the crystal structure of the two molecules is very similar except for a difference in the number of hydrogen bonds they can possibly form, which in turn could affect their structural stability. To test whether HLA-A*0279 has the ability to cross-present A*0201 - restricted peptides to T cells, the full lenght cDNA of HLA-A*0201, -A* 020601 and -A*0279 were respectively transfected into COS-7 cells, which were then used as targets in IFN-gamma release Elispot assay. A*2079 was found to be able to present A*0201- restricted peptides to and induce the response of CTL, thus it can be classified as member of the HLA-A2 functional supertype family. This finding would benefit the design of peptide vaccines to be applied in broader populations.The nucleotide sequence data reported in this paper have been submitted to the Genbank nucleotide sequence database and have been assigned the accession numbers AY856830 and HWS10002813.The name HLA-A*0279 was officially assigned by the World Health Organization Nomenclature Committee in January 2005.     

Genetic Characterization of a new allele of the rabbit group b Ck allotypes

An inherited variant (b4^v) of the rabbit kappa-chain allotype b4 is characterized by the presence of serine in place of alanine at position 121 and leucine in place of glutamine at position 124. The variant was traced through eight generations of a pedigreed rabbit family. Genetic analysis of this trait demonstrated that it is an allele of the other group b allotypes, and recent breedings have produced rabbits homozygous for this light-chain type. Two findings, other than the amino acid sequence differences, distinguish b4^v from b4 in our colony. First, the level of expression of b4^v in heterozygous rabbits is less than that of b4. For example, in b4b4^v rabbits, approximately 30% of the preimmune IgG carries b4^v. In b4^vb5 animals, 46% of the IgG carries the allotype b5, although in animals of allotype b4b5, 38% of the IgG is b5. Second, retrospective analysis of some litters revealed an abnormally low frequency of b4^v in male heterozygotes. However, male b4^vb4^v homozygotes were found at the expected frequency in prospective crosses between b4^vb5 rabbits.For reasons of simplicity the variant will be referred to here as b4^v     

A silent transferrin allele in a Finnish family

In a Finnish family a silent allele was found in the transferrin (Tf) system. As determined by gel electrophoresis and immunoblotting, the Tf type of the father was CD, the mother C, and the child D. The serum Tf concentration in grandmother, mother, and child was less than 50% of normal.     

Seasonality of births and family characteristics in a Spanish population

The seasonality of births in the period 1871-1977 is studied in a rural north-western Spanish population. Based on a total sample of 11,695 birth registrations, temporal variation is analysed. For siblings, according to family reconstitution, the total family size, the legitimacy of the child, and birth order are considered. A coefficient of birth month dispersion is defined and estimated for each family. Intra-family variation is related to inter-family coefficients in order to determine whether the local seasonal pattern of births may be partly explained by family characteristics.     

Characterization of IIB-MEL-J: a new and highly heterogenous human melanoma cell line

A highly heterogeneous cell line, IIB-MEL-J, was established from a human metastatic melanoma. This cell line contains small cells, dendritic cells, and megacells with multiple nuclei. IIB-MEL-J expresses S 100, cytokeratin intermediate filaments and the gangliosides GD2 and GD3. It requires growth factors (insulin, EGF, and transferrin) and antioxidants for optimal growth. When plated under optimal conditions, IIB-MEL-J grows with a doubling time of 70-80 hours. The cells may be fractionated by Percoll gradient centrifugation into several subpopulations (A, B, and C) with different characteristics. Subpopulation A is the slowest growing, and most of the DNA-synthesizing cells are concentrated in fractions B and C. Every subpopulation expresses S 100 and cytokeratin intermediate filaments, whereas only subpopulation B and C express GD2 and GD3. Pigmented cells are concentrated mainly in subpopulation C. Cytogenetic analysis of IIB-MEL-J revealed extensive chromosomal alterations, including a highly heterogeneous chromosome number and chromosomal rearrangements, gains, losses, isochromosomes, and double minutes. This highly heterogeneous cell line may be helpful to study cellular differentiation and interaction between different subpopulations in human melanoma.     

A plasminogen silent allele detected in a Swiss family

An apparent incompatibility between mother and child in the plasminogen system has been clarified by the demonstration of a silent allele in the family.     

HLA-A*02:07 is a protective allele for EBV negative and a susceptibility allele for EBV positive classical Hodgkin lymphoma in China

HLA-A2 protects from EBV+ classical Hodgkin lymphoma (cHL) in Western Europe, but it is unknown whether this protective effect also exists in the Chinese population. We investigated the association of HLA-A2 and specific common and well documented HLA-A2 subtypes with EBV stratified cHL patients (n = 161) from the northern part of China. Quantitative-PCR and sequence-based subtyping was performed to identify HLA-A2 positive samples and their subtypes. 67 (42%) of the cHL patients were EBV+. There were no significant differences in percentages of HLA-A2 positivity between cHL and controls (65% vs 66%) and between EBV+ and EBV− cHL patients (70% vs 61%). The frequency distribution of HLA-A2 subtypes was significantly different between EBV stratified cHL subgroups and controls. This difference was most striking for the HLA-A*02:07 type with a frequency of 38% in EBV+ cHL, 8% in EBV− cHL and 20% in controls. Significant differences were also observed for the HLA-A*02:07, HLA-A2 (non-02:07) and the A2-negative typings between EBV+ cHL vs controls (p = 0.028), EBV− cHL vs controls (p = 0.045) and EBV+ vs EBV− cHL cases (p = 2×10⁻⁵). In conclusion, HLA-A*02:07 is a predisposing allele for EBV+ cHL and a protective allele for EBV− cHL in the northern Chinese population.     

Analysis of allele segregation distortion in a swine resource family

Segregation distortion of alleles was found in several regions of the genome in allele type analyses of genetic markers for a swine resource family that had been constructed by crossing G?ttingen miniature pig and Meishan breeds. From these regions, a region on chromosome 6 presented a distortion over several consecutive markers. This chromosome 6 region was subsequently further investigated to reveal that alleles of a chromosome 6 homologue of the Gottingen miniature pig were not found in a homozygous family member. The litter size of F1-crosses which were able to produce homozygotes in this region were 24% smaller, on average, than F1-crosses which were unable to produce homozygotes. This indicated that this region of the chromosome 6 homologue contained a recessive gene or genes which could terminate fetal development. An additional 10 markers were subsequently used to investigate the region more precisely. These studies revealed that this region spans 7 cM and is located between markers Sw855 and Sw122. Since current comparative maps show that this region corresponds to the human chromosome 19 q-arm, genes positioned on the human chromosome 19 q-arm were screened to select 20 candidate genes. These included the pregnancy-specific beta-1-glycoprotein gene.     

Characterization of a highly repeated DNA family in tapetinae species (mollusca bivalvia: veneridae)

A repetitive DNA family (phBglII400) was characterized in the clam species Tapes philippinarum (Veneridae Tapetinae). The tandemly repeated sequences are AT-rich and show a mainly pericentromeric localization, as most satellite DNAs do. Sequence analysis of phBglII400 DNA family showed a high level of intraspecific homogeneity. Furthermore a 200 bp subunit motif within the 400 bp monomer was apparent as well as the existence of two main "open reading frames" along the 400 bp sequence.In order to investigate the possible distribution of this DNA family among Veneridae, Southern blot analyses were performed on genomic DNAs of Tapes decussatus, Venerupis aurea and Paphia undulata (Tapetinae), Callista chione (Pitarinae), Chamelea gallina (Chioninae) and Venus verrucosa (Venerinae). The phBglII400 family has been found in two additional Tapetinae, namely V. aurea and P. undulata, but not in T. decussatus or other analyzed species. This pattern of sat-DNA distribution supports the high level of differentiation of T. decussatus observed in the previous gene-allozyme analysis. All of these suggest a better allocation of T. decussatus to a genus different from that of T. philippinarum.     

HLA-A*01 allele: a risk factor for dengue haemorrhagic fever in Brazil's population

Severe forms of dengue, such as dengue haemorrhagic fever (DHF) and dengue shock syndrome, are examples of a complex pathogenic mechanism in which the virus, environment and host immune response interact. The influence of the host's genetic predisposition to susceptibility or resistance to infectious diseases has been evidenced in several studies. The association of the human leukocyte antigen gene (HLA) class I alleles with DHF susceptibility or resistance has been reported in ethnically and geographically distinct populations. Due to these ethnic and viral strain differences, associations occur in each population, independently with a specific allele, which most likely explains the associations of several alleles with DHF. As the potential role of HLA alleles in the progression of DHF in Brazilian patients remains unknown, we then identified HLA-A alleles in 67 patients with dengue fever and 42 with DHF from Rio de Janeiro, Brazil, selected from 2002-2008 by the sequence-based typing technique. Statistical analysis revealed an association between the HLA-A*01 allele and DHF [odds ratio (OR) = 2.7, p = 0.01], while analysis of the HLA-A*31 allele (OR = 0.5, p = 0.11) suggested a potential protective role in DHF that should be further investigated. This study provides evidence that HLA class I alleles might be important risk factors for DHF in Brazilian patients.