Extensive nonhomologous meiotic synapsis between normal chromosome axes of an rcp(3;6)(p14;q21) translocation in a hairless Mexican boar

Due to its low fertility, expressed as small litter size, a Mexican hairless boar was subjected to cytogenetic investigation. Analysis of G-banded mitotic chromosomes revealed a reciprocal chromosome translocation, rcp(3;6) (p14;q21). Synaptonemal complex analysis showed a regular pairing behavior of the translocation chromosome axes, always resulting in a quadrivalent configuration. However, due to extensive nonhomologous pairing between the axes of nonderivative chromosomes 3 and 6, the quadrivalent mostly had an asymmetrical cross-shaped morphology. The nonhomologous pairing occurred not only at mid and late pachytene, but also at the earliest stage of pachytene. It seems that early pachytene heterosynapsis is a common phenomenon in the pairing behavior of pig reciprocal translocations. Therefore, heterosynapsis may reduce apoptosis of germ cells due to partial absence of homologous synapsis during the pairing phase of meiosis. The frequency of spermatocytes showing quadrivalent configurations with unpaired axial segments apparently did not affect germ cell progression in the boar, since fairly normal testicular histology was noticed.     

Cloning of the novel gene TM6SF1 reveals conservation of clusters of paralogous genes between human chromosomes 15q24-->q26 and 19p13.3-->p12

As the result of the EUROIMAGE Consortium sequencing project, we have isolated and characterized a novel gene on chromosome 15, TM6SF1. It encodes a 370 amino acid product with enhanced expression in spleen, testis and peripheral blood leukocytes. We have identified another gene, paralogous to TM6SF1 on chromosome 19p12, TM6SF2, with an overall similarity of 68% and 52% identity at the protein level. This conservation has led us to uncover a series of eleven genes in 19p13.3-->p12 with close homology to genes in 15q24--> q26. The percentage of sequence similarity between each paralogous pair of genes at the protein level ranges between 43 and 89%. A partial conservation of synteny with mouse chromosomes 7, 8 and 9 is also observed. The corresponding orthologous genes in mouse of human TM6SF1 and TM6SF2 show a high degree of amino acid sequence conservation.     

Thirteen type I loci from HSA4q, HSA6p, HSA7q and HSA12q were comparatively FISH-mapped in four river buffalo and sheep chromosomes

Thirteen goat BAC clones containing coding sequences from HSA7, HSA12q, HSA4 and HSA6p were fluorescence in situ mapped to river buffalo (Bubalus bubalis, BBU) and sheep (Ovis aries, OAR) R-banded chromosomes. The following type I loci were mapped: BCP to BBU8q32 and OAR4q32, CLCN1 to BBU8q34 and OAR4q34, IGFBP3 to BBU8q24 and OAR4q27, KRT to BBU4q21 and OAR 3q21, IFNG to BBU4q23 and OAR3q23, IGF1 to BBU4q31 and OAR3q31, GNRHR to BBU7q32 and OAR6q32, MTP to BBU7q21 and OAR6q15, PDE6B to BBU7q36 and OAR6q36, BF to BBU2p22 and OAR20q22, EDN1 to BBU2p24 and OAR20q24, GSTA1 to BBU2p22 and OAR20q22, OLADRB (MHC) to BBU2p22 and OAR20q22. All mapped loci appeared to be located on homologous chromosomes and chromosome bands in both bovids. Comparison between gene orders in bovid (BBU and OAR) and human (HSA) chromosomes revealed complex rearrangements, especially between BBU7/OAR6 and HSA4, as well as between BBU2p/OAR20 and HSA6p.     

Intragenic breakpoint within RAD51L1 in a t(6;14)(p21.3;q24) of a pulmonary chondroid hamartoma

Rearrangements involving chromosome region 14q23-->q24 represent a main cytogenetic subgroup in a variety of benign solid tumors. Recently, in uterine leiomyomas containing the classical t(12;14)(q15;q23-->q24), the primary chromosome 14 target gene was identified as the protein kinase-encoding gene RAD51L1. In this report we show that RAD51L1 is also involved in the frequently occurring t(6;14) (p21;q23-->q24) in pulmonary chondroid hamartomas.     

Double partial trisomy of 6p23-pter and 9pter-q21.2 in a neonate resulting from 4:2 meiotic segregation of a maternal complex t(6;7;9)(p23;p15;q21.2) translocation

We report, a newborn presenting multiple congenital abnormalities with karyotype; 47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2--> pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal daughter were carriers of a complex chromosomal rearrangement with karyotypes; 46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case the extra derivative chromosome was the result of a 4:2 segregation of the chromosomes involved in translocation during oogenesis. Double partial trisomy in newborns resulting from 4:2 segregation is a rare event, and double partial trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to date.     

Unbalanced 1q whole-arm translocation resulting in der(14)t(1;14)(q11-12;p11) in myelodysplastic syndrome

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.     

A dysmorphic newborn with 45,X,der(1)inv(1)(p13;qter)t(Y;1)(pter-->q11;p13),-Y de novo karyotype

A dysmorphic newborn with 45,x,der(1)inv(1)(p13;qter)t(y;1)(pter-->q11;p13),-Y de novo karyotype: Y/autosome translocations are very rare chromosomal rearrangements. In most cases, the long arm of the Y chromosome is translocated onto an autosome and most patients are referred because of male infertility. Y/1 translocations are very rare, and have been reported in seven patients so far. Pericentric inversions may be seen in all chromosomes and are not associated with phenotypic abnormalities. Here we report a 6-day old male baby with prenatal growth retardation, frontal bossing, hypertelorism, micrognathia, cleft soft palate, absent uvula, hypospadias, simian line in both hands and hammer toes. Cytogenetic analysis was performed with GTG-banding, C-banding and FISH analysis containing X centromeric probe, Yq12-qter locus specific probe and whole chromosome Y probe. An unbalanced Y/1 translocation was diagnosed: 45,X,der(1)inv(1)(p13;qter)t(Y;1)(pter-->q11;p13),-Y.     

Localization of the human phosphotyrosine phosphatase-related genes (h-PRL-1) to chromosome bands 1p35–p34, 17q12–q21, 11q24–q25 and 12q24

The h-PRL-1 gene codes for a new phosphotyrosine phosphatase that may play an important role in the control of basic cellular processes such as cell growth and proliferation. Using the cDNA of the h-PRL-1 gene as a probe, we examined a somatic mouse and hamster × human hybrid panel and found that chromosomes 1, 17 and 11 harbor sequences homologous to h-PRL-1. By in situ hybridization of metaphase spreads, subchromosomal localizations were determined at bands 1p35–p34, 17q12– q21 and 11q24–q25; in addition, a faint signal was detected at 12q24. The chromosomal assignment of the genes homologous to h-PRL-1 will help the investigation of its possible involvement in human diseases involving genetic alteration at these chromosomal regions. Received: 12 June 1996 / Revised: 27 July 1996     

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.     

Characterization of a complex philadelphia translocation (1p-;9q+;22q-) by gene mapping

Summary Human-Chinese hamster somatic cell hybrids were obtained using circulating leucocytes from a chronic myeloid leukaemia (CML) patient carrying a complex Philadelphia (Ph¹) translocation (1p-; 9q+; 22q-). Hybrid clones which showed segregation of the translocation chromosomes were studied. The chromosome 22 markers ACO2, ARSA, and NAGA segregated with the 1p- derivative; and the chromosome 1 markers UMPK, PGD, and ENO1 segregated with the 9q+ derivative. Hence, molecular evidence has been obtained for the translocation of the distal part of 22q to chromosome 1 and for the translocation of the distal part of 1p to chromosome 9. No conclusions could be drawn either about translocation of chromosome 9 material or about a possible difference in breakpoint in chromosome 22 when compared with six cases of 9;22 translocations similarly studied and previously reported. In addition, a more precise mapping of PGM1 was obtained, the gene being proximal to UMPK and the breakpoint in 1p32.     

Eukaryotic translation termination factor gene (ETF1/eRF1) maps at D5S500 in a commonly deleted region of chromosome 5q31 in malignant myeloid diseases

The human genome contains four ETF1 (eukaryotic translation termination factor 1) homologous sequences, localized on chromosomes 5, 6, 7 and X, and corresponding to a functional gene on chromosome 5 and three processed pseudogenes on the other chromosomes. ETF1 genomic or cDNA probes were mapped by fluorescence in situ hybridization to 5q31, 6p21, 7q11 and Xp11.4-->p11.1. A microsatellite marker (D5S500) was identified in intron 7 of the functional ETF1 gene providing its exact position in the 5q31 band. Thus, the ETF1 gene is located in a 5q region which contains unidentified genes responsible for genetic or malignant disorders, and it might be considered as a candidate gene involved in the pathogenesis of these diseases.     

Allelic losses on chromosomes 1p, 3p, 11p, 11q in non small cell lung cancers

Recent studies have shown that lung cancer patients frequently suffer inactivation of antioncogenes such as Rb gene (13q14) and p53 gene (17p13). In a study of 48 cases of non-small cell lung cancer (28 squamous-cell carcinomas, 11 adenocarcinomas, 4 large-cell carcinomas, and 5 other types) using restriction fragment length polymorphism analysis, we found DNA sequence deletions from chromosomes 1p32-36, 3p21, 11p15.5, and 11q13. The frequencies of allele loss on chromosome 1p, 3p, 11p and 11q are 31, 57, 20 and 49% of informative cases in this patient group, respectively. Of them, 19 tumors show one allele loss and 10 patients suffer two or more allele losses from different chromosomes.     

Assignment of human teratocarcinoma derived growth factor (TDGF) sequences to chromosomes 2q37, 3q22, 6p25 and 19q13.1.

The human teratocarcinoma derived growth factor 1 (TDGF1) gene maps on chromosome (Chr) 3p21.3. One pseudogene (TDGF3) maps on Chr Xq21-->q22. We now report the nucleotide sequence and chromosome location of three additional TDGF pseudogenes. The three new sequences (TDGF2, TDGF4 and TDGF5) are truncated at the 5' end and have accumulated several point mutations, deletions and insertions. TDGF2, TDGF4 and TDGF6 map on Chrs 2q37, 6p25 and 3q22, respectively. Finally, Southern blot analysis of DNA from normal individuals shows a highly variable restriction pattern of the TDGF sequences.     

fra(1) (p11), fra(1) (q22) and r(1) (p11q22) in a retarded girl.

A mentally retarded girl with a 46,XX/47, XX+r(1) (p11q22q22p11)/47, XX+r(1) (p11q22) fra(1) (p31) fra(1) (p11) fra(1) (q22) karyotype who inherited the fragile sites from the normal mother was studied. The conicidence of fra(1) (p11) and fra(1) (q22) with the ring chromosome breakpoints strongly suggests a cause-effect relationship. This finding agrees with other reported associations between fragile sites and structural chromosome abnormalities and constitutes the fourth reported of a de novo structurally abnormal chromosome as a consequence of presumed in vivo fragile sites instability. Although risk figures for chromosome anomalies and cancer associated with fragile sites are lacking, carriers of fra (1) (p11) may have a higher risk for abnormalities of chromosome 1 in somatic and gonadal cells than the general population.     

Interchange trisomy 21 by t(1;21)(p22;q22)mat

Interchange trisomy 21 by t(1:21)(p22:q22)mat: Interchange trisomy 21 by t(1;21)(p22;q22)mat was identified in a sporadic patient with Down syndrome. With a 21q22 specific probe, we observed signals on both normal 21 chromosomes and on the der. We reviewed the 23 published reports of families with reciprocal translocations leading to viable offspring with interchange trisomy 21. The breakpoints in chromosome 21 were mainly located in 21q (19/24 instances, including the present report) and in 19/23 cases the other chromosome involved in the translocation was (pairs 1-12). The underlying 3:1 segregation occurred mainly in carrier mothers; only one patient presented a de novo imbalance and in another case the father was the carrier. In addition, there were 4 instances of concurrence with another unbalanced segregation (adjacent-1 or tertiary trisomy) and 3 families with recurrence of interchange trisomy 21. The mean age of 14 female carriers at birth of interchange trisomy 21 offspring (24.8 yr) was lower that the mean (28.3 yr) found in a larger sample of mothers of unbalanced offspring due to 3:1 segregation (mostly tertiary trisomics) and was not increased with respect to the general population average. Overall, these data agree with previous estimates regarding recurrence risk (9-15%) and abortion rate (about 28%) in female carriers ascertained through an interchange trisomic 21 child.     

Molecular cytogenetic characterization of 17 rob(13q14q) Robertsonian translocations by FISH, narrowing the region containing the breakpoints.

We have characterized 17 rob(13q14q) Robertsonian translocations, using six molecular probes that hybridize to the repetitive sequences of the centromeric and shortarm regions of the five acrocentric chromosomes by FISH. The rearrangements include six de novo rearrangements and the chromosomally normal parents, five maternally and three paternally inherited translocations, and three translocations of unknown origin. The D21Z1/D13Z1 and D14Z1/D22Z1 centromeric alpha-satellite DNA probes showed all rob(13q14q) chromosomes to be dicentric. The rDNA probes did not show hybridization on any of the 17 cases studied. The pTRS-47 satellite III DNA probe specific for chromosomes 14 and 22 was retained around the breakpoints in all cases. However, the pTRS-63 satellite III DNA probe specific for chromosome 14 did not show any signals on the translocation chromosomes examined. In 16 of 17 translocations studied, strong hybridization signals on the translocations were detected with the pTRI-6 satellite I DNA probe specific for chromosome 13. All parents of the six de novo rob(13q14q), including one whose pTRI-6 sequence was lost, showed strong positive hybridization signals on each pair of chromosomes 14 and 13, with pTRS-47, pTRS-63, and pTRI-6. Therefore, the translocation breakpoints in the majority of rob(13q14q) are between the pTRS-47 and pTRS-63 sequences in the p11 region of chromosome 14 and between the pTRI-6 and rDNA sequences within the p11 region of chromosome 13.     

Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3.

Chromosomal assignments of the genes for the human endothelin family, the endothelin-1 gene (EDN1), the endothelin-2 gene (EDN2), and the endothelin-3 gene (EDN3), were accomplished by in situ hybridization to human metaphase chromosomes using a 3H-labeled human preproendothelin cDNA probe for each endothelin. The chromosomal assignment of the EDN2 was also performed by Southern blot analysis of somatic cell hybrid DNAs. EDN1, EDN2, and EDN3 were mapped to 6p23-p24, 1p34, and 20q13.2-q13.3, respectively.     

Translocation breakpoint mapping and sequence analysis in three monosomy 1p36 subjects with der(1)t(1;1)(p36;q44) suggest mechanisms for telomere capture in stabilizing de novo terminal rearrangements

Monosomy 1p36 results from a variety of chromosome rearrangements, including terminal deletions, interstitial deletions, derivative chromosomes, and complex rearrangements. Our previous molecular studies on a large cohort of monosomy 1p36 subjects suggest that a significant percentage of terminal deletions of 1p36 are stabilized by the acquisition of telomeric sequences from other chromosome ends, forming derivative chromosomes (i.e., telomere capture). However, the molecular mechanism(s) that results in and/or stabilizes terminal deletions of 1p36 by telomere capture is poorly understood. In this report, we have mapped the translocation breakpoints in three subjects with der(1)t(1;1)(p36;q44) chromosomes by fluorescence in situ hybridization (FISH). These results indicate that the breakpoint locations are variable in all three subjects, with no common 1p deletion or 1q translocation breakpoints. In addition, sequence analysis of the 1p and 1q breakpoint-containing clones did not identify homologous sequences or low-copy repeats in the breakpoint regions, suggesting that nonallelic homologous recombination did not play a role in mediating these rearrangements. Microsatellite marker analysis indicates that two of the three derivative chromosomes were formed by intra-chromosomal rearrangements. These data are consistent with a number of recent reports in other model organisms that suggest break-induced replication at the site of a double-strand break may act as a mechanism of telomere capture by generating nonreciprocal translocations from terminally deleted chromosomes. Alternative models are also discussed.     

Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region).

The chromosomal localization of the genes coding for the pro-protein and pro-hormone convertases PC1, PC2, and Furin has been achieved by in situ hybridization. The genes for PC1 and PC2 were located on human chromosomes 5q15-21 and 20p11.1-11.2, respectively. The gene for Furin was assigned to the mouse chromosome 7D1-7E2 region. These data complete the chromosomal localization of these three convertases in both human and mouse. The results confirm the regional correspondence of the human chromosomes 15 and mouse chromosomes 7, as well as between human chromosome 20 and mouse chromosome 2. Furthermore, the identification of the NEC1 locus on human chromosome 5 and mouse chromosome 13 suggests a conservation of synthenic regions between these regions of the human and mouse genomes.     

Partial trisomy 13 as a result of de novo (6p;13q) translocation

Summary A newborn infant with the clinical features of the Patau syndrome was found to have excess chromosome 13 material present as a tandem translocation involving the short arm of chromosome 6 and the long arm of an extra chromosome 13: 46,XY,t(6;13)(p24;q12). The major part of the long arm of the extra chromosome 13 was attached linearly (tandem translocation) to the short arm of chromosome 6. Both parents were phenotypically and karyotypically normal.