A refined physical map of the long arm of human chromosome 16

Mapping of 33 anonymous DNA probes and 12 genes to the long arm of chromosome 16 was achieved by the use of 14 mouse/human hybrid cell lines and the fragile site FRA16B. Two of the hybrid cell lines contained overlapping interstitial deletions in bands q21 and q22.1. The localization of the 12 genes has been refined. The breakpoints present in the hybrids, in conjunction with the fragile site, can potentially divide the long arm of chromosome 16 into 16 regions. However, this was reduced to 14 regions because in two instances there were no probes or genes that mapped between pairs of breakpoints.     

Reciprocal translocation between Y chromosome long arm euchromatin and the short arm of chromosome 1

A case with an apparently balanced reciprocal translocation between the long arm of the Y chromosome and the short arm of chromosome 1 t(Y;1)(q11.2;p34.3) is described. The translocation was found in a phenotypically normal male ascertained by infertility and presenting for intra-cytoplasmatic sperm injection treatment. Histological examination of testicular biopsies revealed spermatogenic failure. Chromosome painting with probes for chromosome 1 and for the euchromatic part of the Y chromsome confirmed the translocation of euchromatic Y chromosomal material onto the short arm of chromosome 1 and of a substantial part of the short arm of chromosome 1 onto the Y chromosome. Among the Y/autosome translocations, the rearrangements involving long arm euchromatin of the Y chromosome are relatively rare and mostly associated with infertility. Microdeletion screening at the azoospermia locus revealed no deletions, suggesting another mechanism causing infertility in this translocation carrier.     

Interstitial deletion of long arm of chromosome 13

The case is presented of a patient with the karyotype 46,XX,del(13q)(pter----q22::q32----qter) confirmed by densitometry and a phenotype of mental and growth deficiency, hypotonia, hypertelorism, ptosis, broad nasal bridge, protruding upper incisors, short neck, dislocation of the hip, hypoplasia of the thumbs, fusion of fourth and fifth metacarpal bones and syndactyly of toes. The findings are compared with those of well documented cases with a similar deleted segment of the long arm of chromosome 13. Although it seems obvious that a clinical syndrome for the distal deletion 13q appears to exist more studies with banded chromosomes are needed.     

Fragile site (16) (q22)

Summary The rare autosomal fragile site, fra (16)(q22), is the most common of all rare autosomal fragile sites and has a heterozygote frequency of about 5%. Evidence for it was found following the segregation expected from a simple codominant trait with complete penetrance; this is in contrast to a variety of other rare autosomal fragile sites. Based on the analysis of 12 families in which fra (16)(q22) is segregating, we found that, whereas complete penetrance could be confirmed, the transmitting parent was significantly more likely to be of the female sex. On the other hand, there was no evidence for preferential transmission to offspring of either sex.     

Fine mapping of gene probes and anonymous DNA fragments to the long arm of chromosome 16

The fragile site, FRA16B, at 16q22.100 and four different translocations with breakpoints at 16q22.102, 16q22.105, 16q22.108, and 16q22.3 were used to locate and order DNA probes. This was achieved by Southern analysis of a somatic cell hybrid panel containing portions of chromosome 16 and by in situ hybridization. The anonymous DNA fragments D16S6, D16S10, and D16S11 were proximal to FRA16B and located at 16q13----q22.100. D16S4 and LCAT were located at 16q22.100----q22.102. TAT and HP were located at 16q22.105----q22.108. CTRB was located distal to 16q22.105 and therefore is in the distal half of 16q22. The order of markers in this region was determined as centromere-D16S6, D16S11, D16S10, MT-FRA16B-D16S4, LCAT-HP,TAT,CTRB-APRT- telomere. Linkage studies to determine map distances between the closest markers flanking the fragile site are now in progress.     

Mapping the short arm of human chromosome 16

Physical mapping of 13 different breakpoints on the short arm of chromosome 16 using previously mapped probes and the subsequent mapping of additional probes enabled the division of this portion of the chromosome into six different intervals. D16S94 was mapped between HBA and D16S80 and is closer to PKD1 than either HBA or D16S80. A tight linkage group which includes FRA16A, D16S8, and D16S79 was identified. Seven breakpoints, including FRA16A, could not be separated by probe localizations. This study provides the basis for the development of detailed maps of the short arm of chromosome 16.     

Kinetics of DNA replication in a dicentric X chromosome formed by long arm to long arm fusion

Summary Utilizing the 5-bromo-deoxyuridine (BrdU) incorporation technique, we have recently studied the DNA replication kinetics in a dicentric X chromosome, formed by long arm-to-long arm fusion at band q23, from a 16-year-old black female with primary amenorrhea. The patient has a karyotype 45,X/46,X,dic(X)(q23).In the buccal smear the presence of X chromatin was found in 33% of the cells examined. The Barr bodies are large and 21% of them are bipartite. DNA replication studies were performed on the patient's lymphocytes by the thymidine pulse (T-pulse) method and confirmed comparatively by the BrdU pulse (B-pulse) method. The results indicate that the dicentric X chromosome is always late-replicating. The replication pattern is symmetric on both sides of the breakpoint and the replication sequence is, in order, p11, p22, q1(1–3), q22, q23, p21, and q21. This finding is comparable to those of other investigators and supports the theory that there exist two inactivation centers in the dicentric X chromosome, located on or near the q21 band.     

Interstitial deletion in the long arm of chromosome 7

An interstitial deletion of 7q (q31.2-q32.3) is reported. Main features of this boy included facial dysmorphy, psychomotor retardation and absence of language.     

Interstitial deletion of the long arm of chromosome 3

A patient with multiple congenital malformations and developmental delay is reported. Her karyotype is 46,XX,del(3)(q23q25).     

Interstitial delection of the long arm of chromosome 8

Summary This report describes a polymalformed 18-month-old male with an interstitial deletion of the long arm of chromosome 8. His karyotype is: 46,XY,del(8)(q21).     

Partial deletion of the long arm of chromosome 18

Summary A female infant with mental retardation and multiple somatic anomalies is described. The karyological analysis disclosed the partial deletion of the long arm of chromosome 18 in cells of probands peripheral blood culture. Repeated investigations of probands mothers peripheral blood cultures disclosed the presence of various chromosomal aberrations in 25–70% of cells.     

Interstitial deletion of the long arm of chromosome 7

Summary Chromosome studies were carried out in a girl because of psychomotor retardation and difficulty in swallowing. The girl was admitted to hospital for the first time when 25 months old. The most characteristic signs revealed by the physical examination were short distal ulnar phalanges, clitoral hypertrophy, and very thin outer ear cartilages.An interstitial deletion of the long arm of chromosome 7 was observed: 7q22::7q31.Laboratory investigations revealed a remarkably high level of IgG, immunoglobulin, and an elevated value of serum FSH. No evidence of gene loci located at the deleted part of chromosome 7 were found.     

Interstitial deletion of the long arm of chromosome 11

A female patient with an interstitial deletion of the long arm of chromosome 11 is described. Her growth and psychomotor development were normal. She showed some facial dysmorphic features including cleft lip/palate, a probable cardiac defect and a triphalangeal thumb. A clinical correlation with similar cases is presented.     

Fragile X chromosome and chromosome condensation

The effect of chromosome condensation on the frequency of expression of the fragile X chromosome was examined. Chromosome decondensation substances were tested for their ability to elicit expression or improve frequencies of expression of the fragile X chromosome in five patients. The substances tested included the AT specific DNA ligands ethidium bromide, Hoechst 33258, and netropsin, and the GC specific substances actinomycin D and olivomycin. Under culture conditions appropriate for eliciting fragile X expression none of the decondensation compounds studied significantly altered frequencies of expression, nor did any of the substances elicit fragile X expression under conditions that normally suppress fragile X expression. The fragile X was found to be more frequently evident in less condensed chromosome preparations from fibroblasts. The implications of these findings with respect to the nature of fragile sites are discussed.     

Partial deletion of the long arm of chromosome No. 13

Summary A case of partial deletion of chromosome No. 13 identified by G banding as 46,XX,del(13)(q21-qter) is reported in an infant with severe microcephaly, microphthalmos, talipes calcaneovalgus, and a single crease on each of the little fingers. A review of other cases of chromosome No. 13 deletion that were identified by banding is presented and the correlation between clinical features and deletion of specific bands is discussed.