The incidence of ΔF508 CF mutation,and associated haplotypes,in a sample of English CF families

Summary Data are presented for ΔF508 screening and KM19/XV2c haplotype analysis of 195 cystic fibrosis (CF) chromosomes from the British Caucasian population. We report the frequency of ΔF508 in this group to be 80% and find pronounced disequilibrium between the deletion and the KM 2, XV 1 haplotype. Haplotype analysis of 71 normal chromosomes is also presented. We report one individual who had meconium ileus and who does not have the ΔF508 mutation on either chromosome.     

Association between XV2c/CS7/KM19/D9 haplotypes and the ΔF508 mutation A study of 57 Belgian families

Summary Using Southern blotting and the polymerase chain reaction, the prevalence of the haplotypes for XV2c, CS7, KM19 and D9 on CF and on normal chromosomes could be determined in 35 Belgian families. A set of primers complementary to the DNA sequence of the CF gene around the ΔF508 deletion was used to amplify this particular segment of the gene. In a total of 57 families, deletion screening showed that 69 out of 116 CF chromosomes (59.5%) carried the ΔF508 deletion. Both the ΔF508 deletion and another mutation(s) showed strong association with the haplotype 1-2-2-2.     

Frequency of the F508 deletion in the CFTR gene in Turkish cystic fibrosis patients

Summary The F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene was found in 8 out of 30 Turkish cystic fibrosis (CF) chromosomes (27%). Five Turkish ΔF508 CF chromosomes were associated with the risk haplotype B in KM19 (2 allele)/XV2c (1 allele). In the Turkish population, cystic fibrosis is predominantly caused by mutations other than the F508 deletion.     

Alpha-thalassemia in the four major aboriginal groups in Taiwan

A total of 1309 unrelated blood samples from four major Taiwan aboriginal groups, including 522 of the Ami, 246 of the Bunun, 227 of the Atayal, and 214 of the Paiwan groups, were collected. Subjects with a mean corpuscular volume below 85 fl and Hb A2 values below 3.5% were further studied with Southern hybridization to determine the status of -globin genes. In the Ami, 43 (4.1%) chromosomes had -thalassemia 1 and 43 (4.1%) had -thalassemia 2. Of the 43 -thalassemia 1 chromosomes, 33 were of the Thailand, one of the Philippine, and nine of the Southeast Asian deletion. Of the 43 -thalassemia 2 chromosomes, 42 were of the type I rightward deletion and one was of leftward deletion. In the Bunun group, one chromosome (0.2%) was of the Thailand deletion and two (0.4%) were of type I rightward deletion. In the Atayal group, only one chromosome (0.2%) was of the Philippine deletion. In the Paiwan group, four chromosomes (0.9%) were of the Southeast Asian deletion and three (0.7%) were of the Thailand deletion. Among the four groups, the Ami had the highest prevalence of -thalassemia, which was also higher than that of the Chinese living in Taiwan.     

First analysis of the F508 deletion in cystic fibrosis patients from the GDR

Summary Cystic fibrosis (CF) patients (n = 157) from the GDR were analysed for the occurrence of the recently discovered 3bp deletion causing CF. About 50% of all investigated patients were homozygotes and about 30% heterozygotes for this deletion. Of the analysed CF chromosomes from these patients, 62% carry the deletion, which is in strong linkage disequilibrium with the KM19 restriction fragment length polymorphism allele 2 and the 1/2 XV2c/KM19 haplotype.     

Frequency of the ΔF508 mutation and XV2c,KM19 haplotypes in cystic fibrosis families from The Netherlands: haplotypes without ΔF508 still in disequilibrium

Summary We have determined the frequency of the major cystic fibrosis (CF) three base pair deletion (ΔF508) mutation in 152 CF chromosomes from patients originating from the northern part of The Netherlands. In these patients, the deletion represents approximately 76% of CF mutations. Meconium ileus is strongly associated with homozygosity for the ΔF508 mutation. The XV2c,KM19 haplotypes on the CF chromosomes without the ΔF508 mutation are in disequilibrium with the population frequency, although showing an increased frequency of the 1 2 haplotype. The surplus of this haplotype is almost entirely made up by the pancreatic insufficient patients.     

Origin of an alien disomic addition with an aberrant homologue of chromosome-10 of tomato and its meiotic behaviour in a potato background revealed through GISH

 While characterising potato (Solanum tuberosum, 2n=4x=48) clones with alien tomato (Lycopersicon esculentum) chromosome additions, a single addition for chromosome-10 of tomato was identified through restriction fragment length polymorphism (RFLP) analysis. This plant, 2101–1, was a BC₂ derivative from a cross between a potato (+) tomato fusion hybrid backcrossed to potato. Cytological analysis of its somatic chromosomes through genomic in situ hybridisation (GISH) indicated the presence of four genomes of potato with two alien tomato chromosomes, of which one was much smaller than the other. Analysis of chromosome pairing at the pachytene and metaphase-I stages of microsporogenesis indicated that the large and small chromosomes were homologues. Thus, it was a disomic addition for chromosome-10 of tomato. The size difference was found to be due to a deletion. Fluorescent in situ hybridisation (FISH) experiments, using the telomeric repeat pAtT4 from Arabidopsis thaliana and the sub-telomeric repeat TGRI, showed intact telomeres and sub-telomeres for both alien chromosomes. Thus, the deletion that the smaller of the homologues suffered was interstitial and most probably occurred in the centromeric heterochromatic region of the long arm. The pattern of distribution of large and small chromosomes to telophase-II nuclei during microsporogenesis indicated that the deletion did not affect the meiotic behaviour of the smaller chromosome. In contrast, the frequencies of transmission of the large and the small chromosomes through the female parent, estimated in 96 BC₃ progeny of plants by RFLP and GISH analyses, appeared to be very different, 69.2% and 3.8% respectively. This study also provides evidence that two different chromatids of a pair of homologues, rather than two chromatids of a single chromosome, are most likely to be involved in the origin of a disomic. The aberrant chromosome can be used for the physical mapping of chromosome-10. Received: 9 June 1998 / Accepted: 28 October 1998     

Subtelomeric rearrangements in Polish subjects with intellectual disability and dysmorphic features

Fluorescent in situ hybridization (FISH) was performed in 76 patients referred to our department because of intellectual disability and dysmorphic features that can be related to subtelomeric microaberrations. In all the patients, conventional cytogenetic methods revealed normal karyotype. Four (5.3%) subtelomeric rearrangements were detected by FISH: 2 subtelomeric 1p36 deletions, an unbalanced translocation involving chromosomes 1 and 12 with 1p36 deletion, and a de novo balanced translocation involving chromosomes 19 and 22. Thus, 3 cases of 1p36 subtelomeric deletion were found (3.95%). To confirm subtelomeric rearrangements in 2 patients, comparative genomic hybridization (CGH) was applied. Moreover, 3 cases of polymorphism without phenotypic effects were found: in 2 patients, the polymorphism involved the long arm of chromosome 2 (maternal derivative in both patients), while in the third patient, a polymorphism of the long arm of chromosome 7 was diagnosed. The latter polymorphism was also found in the patient’s mother and grandfather.     

Cytogenetic analysis of sperm from a man heterozygous for a pericentric inversion, inv (3) (p25q21).

Human sperm chromosomes were studied in a man heterozygous for a pericentric inversion of chromosome 3(p25q21). The pronuclear chromosomes were analyzed after in vitro penetration of golden hamster eggs. A total of 144 sperm were examined: 69.2% were chromosomally balanced and 30.8% were recombinant. Of the balanced complements, the proportion with a normal chromosome 3 (37.6%) was approximately equal to the proportion with an inverted 3 (31.6%). Of the recombinant complements, the proportion of sperm with a duplication q/deletion p (17.3%) was approximately equal to the reciprocal event of duplication p/deletion q (13.5%). The recombinant chromosome 3 with a duplication q and deletion p has been observed in several abnormal children, but the duplication p/deletion q has never been reported. My results demonstrate that both recombinant chromosomes are produced as expected from an unequal number of crossovers within an inversion loop. In all likelihood the duplication p/deletion q chromosome is an early embryonic lethal because of the amount of genetic material deleted. The proportions of X-bearing (48.9%) and Y-bearing sperm (51.1%) were not significantly different from the expected 1:1 ratio. There was no evidence for an interchromosomal effect. Of the three inversions studied by human sperm chromosome analysis, recombinant chromosomes have been observed only in this case.     

Molecular data on cystic fibrosis in Bulgaria

Summary A group of 42 cystic fibrosis (CF) patients and 80 heterozygote carriers was analysed for determining the prevalent CF haplotypes and the frequency of ΔF508. The “high-risk” haplotype B (XV2c-KM19/1 2) was found in 66% of CF chromosomes. The prevalent normal haplotypes were A (1 1) and B (2 1). The deletion was detected in 54 CF chromosomes (56%), homozygotes constituting 35% of all CF patients. In 88% of cases the mutation was linked to haplotype B, and in 12% to haplotype D (2 2). Chromosomes that did not have ΔF508 were found to be evenly distributed among all four XV2c-KM19 haplotypes. The use of restriction fragment length polymorphisms and direct detection of the mutation makes 94% of CF families fully informative for prenatal analysis.