Continuous linkage map of human chromosome 14 short tandem repeat polymorphisms.

Nine moderately to highly informative short tandem repeat polymorphisms were assigned to chromosome 14 using somatic cell hybrids and were mapped using linkage analysis. The nine markers formed a continuous linkage map covering almost the entire long arm from 14q11.2 to q32. The markers filled a large gap within previously reported linkage maps for this chromosome. Best order of the new loci from q11.2 to q32 was D14S50, D14S54, D14S49, D14S47, D14S52, D14S53, D14S55, D14S48, and D14S51. The order shown for all adjacent pairs of loci was very strongly favored with the exception of loci pair D14S55 and D14S48, for which the order was moderately favored. Map lengths for the nine loci were 142 cM in females and 72 cM in males. Female recombination frequencies exceeded male recombination frequencies in the middle and distal portions of the map.     

Growth of large chromosomally abnormal T cell clones in ataxia telangiectasia patients is associated with translocation at 14q11

Summary Human T cell malignancies often show chromosome breaks at 14q11, within the chain locus of the human T cell antigen receptor, with translocation of the distal portion of 14 to one of several sites. In patients with ataxia telangiectasia (A-T) the majority of T cell chromosome translocations associated with this disorder appear to occur at the sites of the T cell antigen receptor genes 7p14, 7q35, and 14q11 and may result in clone formation. In three large proliferating A-T T cell clones we have observed (including one which became malignant) and in most T cell tumours reported, the clonal chromosome exchange involves one breakpoint at 14q11 with the second breakpoint occurring in a gene not involved in the immunoglobulin supergene family. Our observations on A-T patients confirm the suggestion that chromosome exchanges involving either t(7;14)(p14;q11), t(7;14)(q35;q11), inv(7) (p14q35), or t(7;7)(p14;q35) confer only a small proliferative advantage on T cells in vivo without the capacity for malignant transformation and that the potential for malignant change is not a feature of all these rearrangements, but is restricted to cells or clones with other chromosome exchanges.     

High rate of detection of 13q14 deletion mosaicism among retinoblastoma patients (using more extensive methods)

Summary Using a cell population with a high proportion of early mitotic cells and by examining more cells derived from peripheral lymphocytes, we found three cases with a 13q14 deletion mosaicism among fifteen retinoblastoma patients; one with a de novo 13/18 balanced translocation, and another with a monosomy 13(q13»q21.2 or 21.3). The three patients with a 13q14 deletion mosaicism had sporadic retinoblastoma (two had bilateral and one unilateral retinoblastoma). The results indicate that 13q14 deletion mosaicism plays a major role in the etiology of this tumor.     

A chromosome 14-specific human satellite III DNA subfamily that shows variable presence on different chromosomes 14.

We describe a new subfamily of satellite III DNA (pTRS-63), which, by a combination of in situ hybridization to human metaphase chromosomes and analysis of a panel of somatic cell hybrids, is shown to be specific for human chromosome 14. This DNA has a basic 5-bp repeating unit of diverged GGAAT which is tandemly repeated and organized into either one of two distinct higher-order structures of 5 kb (designated the "L" form) or 4.8 kb (designated the "S" form). In addition, a third (Z) form, representing no detectable levels of this satellite III subfamily, is found. Results from five somatic cell hybrid lines and from a number of informative human individuals suggest that, on any one chromosome 14, only one of the three forms may exist. Subchromosomally, this sequence has been mapped to the p11 region and is distal to the domain occupied by another previously described satellite III subfamily (pTRS-47) found on chromosome 14. The pTRS-63 sequence described adds to the understanding of the structural organization of the short arm of human chromosome 14 and should be useful for the investigation of the molecular etiology of the frequently occurring t(13q14q) and t(14q21q) Robertsonian translocations.     

Molecular cloning of a DNA fragment from human chromosome 14(14q11) involved in T-cell malignancies.

To isolate DNA segments specific to chromosome band 14q11, which has been implicated in a number of human T-cell malignancies, a genomic DNA library was prepared from a variant cell subline of the human lymphoblastic KE37 cell line. This subline (KE37-R) bears a t(8;14) (q24;q11) translocation, and the breakpoint on the resulting chromosome 8q+ has been located at the 3' end of the third c-myc exon. Three molecular clones were isolated by screening the library with a c-myc exon 3 probe, and one of them (lambda K40) was analyzed in detail. It contains a 15-kb insert consisting of 4.5 kb of sequence from chromosome 8 (e.g., downstream of c-myc exon 3) and sequences from chromosome 14. The origin of these latter sequences was established by hybridizing DNA from chromosomes sorted by flow cytometry to a lambda K40 subclone containing only chromosome 14 presumptive sequences and by Southern blot analysis of rodent X human somatic hybrid cell DNA with the same probe. No cross-hybridization was found between the lambda K40 clone and a cDNA clone for the alpha chain T-cell receptor gene which is also located in 14q11. A preliminary survey of DNAs from human T-cell malignancies with a probe corresponding to chromosome 14 sequences of lambda K40 clone revealed for some of them restriction patterns different from those of the germ line DNA. The fact that the rearrangement observed in a leukemic patient was not found in DNA from lymphocytes obtained during remission excluded any polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)     

A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q13-->q24.1 and partial monosomy 4q27-->q28 [corrected

Complex chromosomal rearrangements (CCRs) are usually associated with infertility or subfertility in male carriers. If fertility is maintained, there is a high risk of abnormal pregnancy outcome. Few male carriers have been identified by children presenting with mental retardation/congenital malformations (MR/CM) or by spontaneous abortions of the spouses. We report a de novo CCR with five breakpoints involving chromosomes 4, 10 and 14 in a male carrier who was ascertained through a son presenting with MR/CM due to an unbalanced karyotype with partial trisomy 14 and partial monosomy 4. The child has a healthy elder brother. In the family history no abortions were reported. No fertility treatment was necessary. Cytogenetic analysis from the affected son showed a reciprocal translocation t(4;10) with additional chromosomal material inserted between the translocation junctions in the derivative chromosome 10. The father showed the same derivative chromosome 10 but had additionally one aberrant chromosome 14. Further molecular cytogenetic analyses determined the inserted material in the aberrant chromosome 10 as derived from chromosome 14 and revealed a small translocation with material of chromosome 4 inserted into the derivative chromosome 14. Thus the phenotype of the son is supposed to be associated with a partial duplication 14q13-->q24.1 and a partial monosomy 4q27-->q28. Including our case we are aware of eleven CCR cases with fertile male carriers. In eight of these families normal offspring have been reported. We propose that exceptional CCRs in fertile male carriers might form comparatively simple pachytene configurations increasing the chance of healthy offspring.     

13q14断裂重排与非小细胞肺癌转移潜能关系的研究

肿瘤转移的细胞经常存在染色体数目异常和结构畸变,在多种有转移潜能的肿瘤细胞中都涉及到13q14的异常。以往研究表明在同一组织来源但转移潜能不同的肺腺癌细胞系AGZY83-a和Anip973中存在13q14的断裂重排。采用mRNA差异展示技术（mRNA DD）分析这一对细胞系得到的差异表达基因BRI基因位于13q14。为了进一步分析肺癌细胞的转移潜能与13q14断裂重排间的关系,采用13q涂染探针对具有不同转移潜能的非小细胞肺癌细胞系PAa、SPC-1-A和95D中期分裂相进行G显带后的荧光原位杂交分析。结果发现在3个肺癌细胞系中有多种13号染色体长臂的结构异常,其中此3个细胞系均涉及13q32-33的频发断裂。但是低转移肺癌细胞系PAa、SPC-1-A均未涉及13q14的断裂,而高转移肺癌细胞系95D的两种细胞克隆均可见13q14的断裂。提示13q14断裂点与肺癌细胞的转移能力有一定的相关性,两者之间的遗传学意义需要进一步研究探索。     

The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma

Summary The T cell receptor chain gene locus and the immunoglobulin heavy chain gene locus (IgH) have previously been mapped to the q11 and q32 positions respectively of the human chromosome 14. Both of these sites are also common breakpoints in lymphocytes from ataxia telangiectasia (A-T) patients. Using in situ hybridisation we show that the 14q32 breakpoint in an A-t non-leukaemic T cell clone with t(14;14) translocation, lies outside the IgH locus and proximal to it with respect to the centromere. The 14q11-14qter segment of the homologous chromosome 14 carrying the constant gene region of the chain locus is translocated to this 14q32 position.     

Partial trisomy of the distal segment of 14q

Summary The case of a male infant with duplication of the distal segment of chromosome 14q is described. There was an extra chromosomal segment at the distal end of the long arm of chromosome 17. Banding techniques suggested that the extra segment might be the distal segment of chromosome 14q. DNA analysis using probes from distal 14q as well as from other parts of the genome confirmed that the extra segment consisted of the distal part of 14q. Both the proband's parents and his elder sister had normal karyotypes.     

Distal trisomy 14q

Two cases of de novo duplication of the distal part of the long arm of chromosome 14 are reported. In one case, the partial trisomy of 14q is due to translocation of a segment (14q24 to 14qter) at the end of the satellite stalk of chromosome 14. The clinical picture is very severe. In the second case, a tandem duplication in 14 (q23----q32) is present with only minor malformations and mild mental retardation.     

Distal trisomy 14q

Summary Two cases of chromosome 14 rearrangements with partial duplication which occurred de novo were analyzed by Southern blot analysis using IGH, D14S1 and PI probes. In the first case, with a 46,XX,14p+ karyotype, our study confirms that the additional material on chromosome 14p+ results from a duplication of the 14q region containing the IGH, D14S1 and PI loci. In the second case, our study reveals only one 14q32 locus per chromosome 14 indicating that the extra material does not contain the 14q32 region. Our results demonstrate that molecular probes of the 14q32 region are valuable tools for the characterisation of chromosome 14 abnormalities appearing de novo.     

A case of segmental paternal isodisomy of chromosome 14

Uniparental disomy of chromosome 14 (UPD 14) results in one of two distinct abnormal phenotypes, depending upon the parent of origin. This discordance may result from the reciprocal over-expression and/or under-expression of one or more imprinted genes. We report a case of segmental paternal isodisomy for chromosome 14 with features similar to those reported in other paternal disomy 14 cases. Microsatellite marker analysis revealed an apparent somatic recombination event in 14q12 leading to proximal biparental inheritance, but segmental paternal uniparental isodisomy distal to this site. Analysis of monochromosomal somatic cell hybrids containing either the paternally inherited or the maternally inherited chromosome 14 revealed no deletion of the maternally inherited chromosome 14 and demonstrated the presence of paternal sequences from D14S121 to the telomere on both chromosomes 14. Thus, the patient has paternal isodisomy for 14q12-14qter. Because the patient shows most of the features associated with paternal disomy 14, this supports the presence of the imprinted domain(s) distal to 14q12 and suggests that the proximal region of chromosome 14 does not contain imprinted genes that contribute significantly to the paternal UPD 14 phenotype.     

Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32.

T-cell tumours are frequently found to carry an inversion of chromosome 14 (inv(14)) (q11;q32) or more rarely a chromosome 14 translocation t(14;14) with the same cytogenetic breakpoints (q11;q32). We have examined the molecular junctions of an inv(14) and a translocation t(14;14) using T-cell receptor (TCR) alpha joining (J) region probes. Both of these chromosomal abnormalities have breakpoints within the TCR J alpha locus at 14q11 and both have breakpoints which are proximal (i.e. on the centromeric side) to the immunoglobulin heavy chain JH region at 14q32. The cloned segments corresponding to the junctions at 14q32 are not associated with obvious immunoglobulin-like sequences. This contrasts to the previously described inv(14) in the cell line SUP-T1 and places a potential cluster of chromosome 14 breakpoints downstream of the Ig JH locus. The possible role of the varying breakpoints in the development of these tumours is discussed.     

Pure partial trisomy 5q33-->5q35 resulting from the adjacent-1 segregation of a paternal (5;14)(q33;p12) translocation.

A 14-year-old male was referred for evaluation of mental retardation with short stature and dysmorphic features. His karyotype was 46,XY,der(14)t(5;14)(q33;p12)pat, resulting in a pure partial 5q33-q35 trisomy due to the adjacent-1 segregation of a paternal balanced translocation. Paternal blood karyotype revealed a balanced translocation t(5;14)(q33;p12) retaining Ag-Nors. To date, only two cases of pure partial 5q trisomies spanning this region have been reported. Analysis of these cases and the one we report does not allow the delineation of a specific phenotype.     

Localization of the restriction fragment length polymorphism D14S1 (pAW-101) to chromosome 14q32.1 leads to 32.2 by in situ hybridization

The restriction fragment length polymorphism D14S1 is delineated by the cloned, single-copy DNA fragment pAW-101. This cloned fragment can therefore serve as a useful marker for gene linkage studies, and the exact location on the gene map is of great interest. pAW-101 was 3H-labeled and hybridized in situ to normal, prometaphase chromosome preparations. Analysis of the grain distribution shows this fragment to be localized to the long arm of chromosome 14 at band q32. Using lymphoid cell lines with 8;14 reciprocal translocations (q24.1;q32.3) from patients with Burkitt lymphoma, we found that the DNA fragment hybridizes to the rearranged chromosome 14 proximal to the breakpoint. These results localize D14S1 to the region 14q32.1 leads to 32.2 This is consistent with localization of this fragment utilizing somatic cell hybrids and family studies.     

Infertility in human males with autosomal translocations: meiotic study of a 14;22 Robertsonian translocation

Summary Pachytene analysis was undertaken in a male patient heterozygous for a 14q22q Robertsonian translocation. The relatively low rate of XY autosome association led us to examine the relationships existing between the chromosomes involved in the translocation, the rate of XY-autosome association and the degree of spermatogenic failure. Cytogenetic investigations in infertile men and the results of the meiotic studies suggest a direct correlation between the frequency of XY-autosome association at pachytene and the degree of spermatogenic failure. Whether associations arise as a consequence or cause of germ cell failure is still not certain.     

Exceptional complex chromosomal rearrangement and microdeletions at the 4q22.3q23 and 14q31.1q31.3 regions in a patient with azoospermia

In this report we describe the first patient ever found to have azoospermia in association with both exceptional complex chromosomal rearrangements and microdeletions at two translocation breakpoints. A 36-year-old male who had been suffering from male factor infertility was admitted to our clinic. The patient also displayed mild dysmorphia. An analysis of the patient's semen revealed azoospermia. GTG banding revealed the presence of an exceptional complex chromosomal rearrangement involving chromosomes 1, 4, 10 and 14. Using subtelomeric FISH analysis, the patient's karyotype was designated as 46,XY,t(1;10)(q43q44;q21q26.1)(CEB108/T7+,D1S3738-;10PTEL006+,D10S2290+, D1S3738+), ins(14;4) (q31.3;q23q33)(D14S1420+; D4S3359+, D4S2930+). Array-CGH analysis revealed two microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions. We suggest that microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions associated with both an exceptional complex chromosomal rearrangement and the Homo sapiens chromosome 4 open reading frame 37 (C4orf37) gene located at the 4q22.3q23 region might be associated with male factor infertility.     

Partial duplication 14q/deletion 2q in two sibs due to t(2;14) (q37.1;q31.2) pat

Two siblings are described with duplication 14q/deletion 2q due to a paternal translocation (2;14) (q37.1;q31.2). The first one, a boy, born at term, lived 14 days. The second one, a female foetus, was born after induced labour when the anomaly was discovered by way of amniocentesis. They both had almost identical phenotypes. From a study of the literature it is inferred that a typical asymmetric head form, low set abnormal ears, micrognathia, long upper lip, rib anomalies, camptodactyly, long fingers and contractures are prominent features of the syndrome.     

Partial trisomy 14q due to familial t(14q-, 11q+) translocation

Summary A malformed male newborn with partial trisomy for the distal part of the long arm chromosome 14 (14q₂₃14qter) is described. This anomaly arose as a segregation product of a balanced t(14q-, 11q+), translocation in the father.     

Paracentric inversion of chromosome 14 plus rare 9p variant in a couple with habitual spontaneous abortion.

A couple presenting with habitual spontaneous abortion both showed a chromosome rearrangement. The male had an apparently balanced paracentric inversion of chromosome 14 - 46,XY,inv(14) (q11q32). The female had a karyotype with a rare large short arm variant of chromosome 9 - 46,XX,var(9) (p11p21). Testing of a living normal child showed that he had inherited both rearrangements. Family testing showed the chromosome 9 variant in three generations, with all carriers being of normal phenotype and intelligence. This study confirms that the presence of more than one chromosomal rearrangement can be compatible with normal development. This is useful for genetic counselling. Nevertheless when such cases arise, each must be individually assessed.