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PubMed1993

Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder in Langer-Giedion syndrome.

Fifteen cosmids containing sequences from the human bone morphogenetic protein 1 gene (BMP1) were isolated from a cosmid library. The probe was a 483-bp DNA obtained by the reverse transcriptase-PCR method using primers designed according to the reported BMP1 sequence. When the positive cosmids were tested for chromosome fluorescence in situ hybridization, all showed signals at 8p21. The results indicated that BMP1 is not responsible for Langer-Giedion syndrome, whose putative gene has been assigned to 8q24.

Base Sequence↗
PubMed1995

Assignment of the uteroferrin gene (ACP5) to swine chromosome 2q12-->q21 by fluorescence in situ hybridization.

A cosmid clone containing the uteroferrin gene (ACP5) was selected from a cosmid library of swine genomic fragments by colony hybridization using uteroferrin cDNA as a probe. The genomic fragment thus cloned was examined by Southern blot and sequence analysis which demonstrated that it contained at least a part of the uteroferrin gene. The cosmid clone DNA was labeled with biotin, and used a probe for in situ hybridization to swine chromosomes. Hybridization was visualized by the FITC-labeled streptavidin/biotinylated antistreptavidin system together with R-banding of chromosomes. The hybridization signals revealed that the uteroferrin gene (ACP5) is located on swine chromosome 2q12-->q21.

Acid Phosphatase↗
PubMed1996

FISH detection of chromosome polymorphism and deletions in the spinal muscular atrophy (SMA) region of 5q13.

The search for the SMA defect has culminated in the identification of two candidate 5q13.1 SMA genes, NAIP and SMN both of which are deleted in individuals with SMA. It was postulated that the intact and degenerate versions of NAIP are present in variable and frequently high copy numbers in this region while SMN was proposed to be present in only two copies. In order to assess the copy number of NAIP and SMN we have conducted interphase FISH analysis using NAIP and SMN gene-containing cosmid and plasmid probes. Our results confirm the variability in the number of NAIP signals in non-SMA chromosomes (2-6) and show that SMN is present on average twice per chromosome although in one chromosome 4-5 signals for the SMN-containing cosmid probe were detected. Our analysis reveals that one of four and three of six type I SMA chromosomes had a lower than normal number of NAIP and SMN signals, respectively. In two of six SMA type I chromosomes, complete loss of hybridization signal was observed on one chromosome 5 with our SMN cosmid probe possibly reflecting a large scale deletion. Large scale deletions were not detectable when metaphase chromosomes of an SMA type II and III patient were analyzed.

Chromosome Deletion↗
PubMed1997

Mapping of the 8q12 translocation breakpoint to a 40-kb region in a pleomorphic adenoma with an ins(8;3)(q12;p21.3p14.1).

The translocation t(3;8)(p21;q12) is the most common chromosome abnormality observed in pleomorphic adenomas of the salivary glands. In this paper we describe the physical mapping of the breakpoints in an adenoma with a variant t(3;8), viz., an ins(8;3)(q12;p21.3p14.1). Using sequence-tagged sites (STSs) corresponding to landmarks within a previously identified yeast artificial chromosome (YAC) spanning the breakpoint in adenomas with t(3;8), cosmids isolated from a chromosome 8-specific cosmid library. The 8q12 insertion breakpoint was mapped by FISH to a 300-kb region flanked by MOS and a new STS, CH129. A cosmid within this region was shown to span the breakpoint. To test whether the recently identified FHIT gene, which maps to 3p14.2, was disrupted by the 3p rearrangement, we also isolated an FHIT YAC and mapped this YAC by FISH distal to the most proximal 3p breakpoint. In addition, RT-PCR analysis revealed only a normal-sized FHIT transcript, suggesting that FHIT is not affected by the 3;8-rearrangement.

Adenoma, Pleomorphic↗
PubMed1997

Development of diagnostic tools for the analysis of 5p deletions using interphase FISH.

Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5. Through the phenotypic and molecular analyses of individuals with a subset of the features associated with the syndrome, the genes involved in the syndrome have been mapped to two distinct critical regions. Deletion of a critical region in 5p15.2 results in the distinct facial features associated with the syndrome as well as the severe mental and developmental delay, while a deletion of 5p15.3 is associated only with the characteristic cat-like cry, the key diagnostic feature of the syndrome. Therefore, subtle differences in the extent of the 5p deletion can have a profound affect on the prognosis of the patient. In order to more easily differentiate between deletions that lead to the cri-du-chat syndrome phenotype and deletions that lead only to the isolated cat-like cry, we have constructed YAC contigs that span both critical regions. The YAC clones have been used to isolate cosmids mapping to each critical region and cosmids that lie just within the two critical region boundaries have been identified. We report here on the use of these cosmids as probes for fluorescent in situ hybridization experiments on interphase nuclei as a means of more accurately differentiating between small 5p deletions that coincide with a complete cri-du-chat syndrome phenotype and the severe mental and developmental delay that is associated with it and deletions that only delete the distal critical region that coincide with the isolated cat-like cry and a much improved prognosis.

Animals↗
PubMed1996

Genomic structure of a Y-specific ribonucleic acid binding motif-containing gene: a putative candidate for a subset of male infertility.

The genetic basis of infertility remains unclear in a majority of infertile men. Deletion mapping studies suggest that genes on the long arm of the Y-chromosome (Yq) may be important in the spermatogenic process and may play a pathogenetic role in a subset of infertile men. Complementary DNA sequences of two Y-specific genes that contain ribonucleic acid binding motifs and, therefore, referred to as RBM genes (previously named YRRM) were published recently. To develop a PCR-single strand conformation polymorphism strategy for detection of point mutations in the RBM gene(s) in infertile men, we determined the genomic structure and flanking sequences at the intron-exon junctions. Two separate strategies were used in parallel to isolate the genomic fragment bearing the RBM gene. The first strategy employed screening of a P1 genomic library using PCR primers corresponding to the sequences in the 5'- and 3'-ends of the published RBM-1 complementary DNA sequence. The second strategy used subcloning of the YAC clone 925D10 (that contained the RBM gene described here) into cosmids. The P1 and cosmid clones were further restriction mapped and subcloned for DNA sequencing. Because the sequences contained in the P1 and cosmid clones were identical, the sequence information was pooled. A 15-kilobase genomic segment includes the entire RBM gene. The genomic structure of this RBM gene is characterized by 12 exons and 11 introns. There is considerable homology among exons VII, VIII, IX, and X; each encodes one of the SRGY boxes. Several introns also have a high degree of homology among them (introns VI, VII, VIII, and IX). Eleven of the 12 exons have complete sequence homology with the RBM-1 sequence. There is 1 base difference in exon IV at position 495 (a T in the previously published DNA sequence vs. an A in the sequence reported here). The exonic sequences of this gene are distinct from that of the RBM-2 gene. The flanking sequences at the exon-intron junctions were also determined and are reported. Reverse transcription-PCR analysis, using human testis ribonucleic acid suggests that this gene is either not expressed in the testis or, more likely, the single base difference from RBM1 represents a polymorphism in the YAC clone. A high degree of homology between intronic and exonic sequences within the same gene and between different members of the RBM gene family (data not reported in this paper) suggests origin from common ancestral sequences; this also indicates that development of a single strand conformation polymorphism approach for detection of point mutations is likely to prove difficult for some of the exons of this gene.

Base Sequence↗
PubMed2004

Marker-based cloning of the region containing the UhAvr1 avirulence gene from the basidiomycete barley pathogen Ustilago hordei.

Race-cultivar specialization during the interaction of the basidiomycete smut pathogen Ustilago hordei with its barley host was described in the 1940s. Subsequent genetic analyses revealed the presence of dominant avirulence genes in the pathogen that conform to the gene-for-gene theory. This pathosystem therefore presents an opportunity for the molecular genetic characterization of fungal genes controlling avirulence. We performed a cross between U. hordei strains to obtain 54 progeny segregating for three dominant avirulence genes on three differential barley cultivars. Bulked segregant analysis was used to identify RAPD and AFLP markers tightly linked to the avirulence gene UhAvr1. The UhAvr1 gene is located in an area containing repetitive DNA and this region is undetectable in cosmid libraries prepared from the avirulent parental strain. PCR and hybridization probes developed from the linked markers were therefore used to identify cosmid clones from the virulent (Uhavr1) parent. By walking on Uhavr1-linked cosmid clones, a nonrepetitive, nearby probe was found that recognized five overlapping BAC clones spanning 170 kb from the UhAvr1 parent. A contig of the clones in the UhAvr1 region was constructed and selected probes were used for RFLP analysis of the segregating population. This approach genetically defined an approximately 80-kb region that carries the UhAvr1 gene and provided cloned sequences for subsequent genetic analysis. UhAvr1 represents the first avirulence gene cloned from a basidiomycete plant pathogen.

Base Sequence↗
PubMed2001

[Social exchange and inference: an experimental study with the Wason selection task].

Social contract theory (Cosmides, 1989) posits that the human mind was equipped with inference faculty specialized for cheater detection. Cosmides (1989) conducted a series of experiments employing the Wason selection task to demonstrate that her social contract theory could account for the content effects reported in the literature. The purpose of this study was to investigate the possibility that the results were due to experimental artifacts. In the current experiment, the subject was given two versions of the Wason task that contained no social exchange context, but included an instruction implying him/her to look for something, together with the cassava root and the abstract versions used by Cosmides (1989). Results showed that the two versions with no social exchange context produced the same response pattern observed in the original study. It may be concluded that the subject's perception of the rule as a social contract was not necessary to obtain the original results, and that an instruction implying that he/she should look for something was sufficient.

Humans↗
PubMed1999

Transgenic analysis of a 100-kb human beta-globin cluster-containing DNA fragment propagated as a bacterial artificial chromosome.

To date, the normal transcriptional regulation of the human beta-globin gene cluster has been recapitulated most accurately in transgenic mice that carry large yeast artificial chromosome (YAC) or ligated cosmid constructs. However, these large transgenes still exhibit variegated expression levels, perhaps because they tend to rearrange upon integration, or because the cloning vectors remain attached to the globin inserts. To try to circumvent these potential problems, we investigated the transgenic properties of a 100-kb DNA fragment containing the entire human beta-globin cluster propagated in a bacterial artificial chromosome (BAC). We created 9 independent mouse lines, each carrying 1 to 6 copies of the human beta-globin cluster without the attached BAC vector. Five of the lines carry unrearranged copies of the cluster. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of adult F(1) mice showed that 2 lines express human beta globin at levels approximately equivalent to the endogenous mouse beta-major genes. One line expresses no human beta globin, while the remaining 6 lines show intermediate expression levels. Complete gamma-->beta-globin gene switching occurs, but is slightly delayed with respect to the endogenous mouse embryonic-->adult switch. Since these data are similar to what has been obtained using globin YACs or ligated cosmids, we conclude that (1) globin transgenes propagated in BACs are no less likely to rearrange than their cosmid or YAC counterparts, and (2) the retention of YAC vector sequences in a transgene probably has no significant impact on globin expression when using constructs of this size.

Animals↗
PubMed2000

Defining a common region of DNA amplification at 22q11.2-12 in head and neck squamous cell carcinomas by quantitative FISH analysis.

By comparative genomic hybridization (CGH) with 17 head and neck squamous cell carcinoma (HNSCC) cell lines, we previously detected an amplified region as a distinct peak at 22q11.2-12 in 3 cell lines. Because the possible presence of an oncogene was strongly suggested, the region was mapped in more detail by defining the minimum region that was commonly amplified by using fluorescence in situ hybridization (FISH) with a series of cosmids. Eighteen cosmid clones on 22q11.2-12 were assigned to their locations as a fractional length map and hybridized to cells from three HNSCC cell lines. The three cosmid clones, cHKA-118, cHKAD-26, and D22S938, showed the highest levels of amplification, and the size of the amplicon was calculated to be approximately 1.7 Mb in the OM1 and HSC6 cell lines. Several genes related to oncogenesis, including PRKM1, map to this locus. Thus, the definition of the common region with the highest level of copy number increases by FISH provides a starting point for identifying the gene that may play an important role in the development of HNSCC.

Carcinoma, Squamous Cell↗
PubMed2001

Selection of several classes of mimosine-degradation-defective Tn3Hogus-insertion mutants of Rhizobium sp. strain TAL1145 on the basis of mimosine-inducible GUS activity.

Rhizobium sp. strain TAL1145 that nodulates Leucaena leucocephala degrades mimosine, a toxin produced by this tree legume. A cosmid clone, pUHR263, containing approximately 25 kb cloned DNA was isolated by plating Escherichia coli cells containing the cosmid clone library of TAL1145 on a minimal medium in which 3-hydroxy-4-pyridone (HP), a degradation product of mimosine, was used as the source of nitrogen. Cosmid pUHR263 was mutagenized by random insertions of Tn3Hogus, a transposon that makes transcriptional gus fusions when it is inserted in a gene in the correct orientation. Various pUHR263::Tn3Hogus derivatives that showed mimosine-inducible or mimosine-repressible GUS activities when transferred to the Rhizobium sp. strain TAL1145 were selected. Mutants of TAL1145 were constructed by transferring these Tn3Hogus insertions into the TAL1145 chromosome through double-homologous recombination. These mutants were classified into five classes on the basis of defects in mimosine degradation. The growth of these mutants was inhibited to different extents by mimosine applied to the growth medium. Mimosine forms a red-colored Fe-mimosine complex when FeCI3 is added to the medium. The inhibitory effect of Fe-mimosine on growth of the mutants was much less than that of mimosine.

Bacterial Proteins↗
PubMed1992

Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.

Fluorescence in situ hybridization (FISH) with biotin-labeled probes mapping to 11p13 has been used for the molecular analysis of deletions of the WAGR (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) locus. We have detected a submicroscopic 11p13 deletion in a child with inherited aniridia who subsequently presented with Wilms tumor in a horseshoe kidney, only revealed at surgery. The mother, who has aniridia, was also found to carry a deletion including both the aniridia candidate gene (AN2) and the Wilms tumor predisposition gene (WT1). This is therefore a rare case of an inherited WAGR deletion. Wilms tumor has so far only been associated with sporadic de novo aniridia cases. We have shown that a cosmid probe for a candidate aniridia gene, homologous to the mouse Pax-6 gene, is deleted in cell lines from aniridia patients with previously characterized deletions at 11p13, while another cosmid marker mapping between two aniridia-associated translocation breakpoints (and hence a second candidate marker) is present on both chromosomes. These results support the Pax-6 homologue as a strong candidate for the AN2 gene. FISH with cosmid probes has proved to be a fast and reliable technique for the molecular analysis of deletions. It can be used with limited amounts of material and has strong potential for clinical applications.

Adult↗
PubMed1992

Deletions of chromosome 5 in malignant myeloid disorders.

Loss of a whole chromosome 5 or deletion of 5q are recurring abnormalities in malignant myeloid neoplasms. Chromosomal loss or deletion are the hallmarks of tumour suppressor genes, suggesting that a gene(s) located on 5q may function as a leukaemia suppressor gene. To determine the location of genes on 5q that may be involved in myeloid leukaemogenesis, we examined the breakpoints of the del(5q) in a series of 117 patients with malignant myeloid diseases. By comparing the breakpoints, we identified a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. A striking number of genes encoding haematopoietic growth factors have been mapped within or adjacent to the critical region. These include the genes encoding CSF-2, IL-3, IL-4, IL-5 and IL-9. By using fluorescence in situ hybridization, we have refined the localization of these genes to 5q31.1. To facilitate the identification of a tumour suppressor gene on 5q, we are currently preparing a physical map of 5q31. With FISH analysis of a series of cosmid and phage clones, we identified a number of clones within 5q31. By hybridizing these probes to metaphase cells with a del(5q) involving proximal or distal breakpoints within 5q31, we have narrowed the critical region to a small segment of 5q31 containing eight of the cosmids. In addition, we found that the five growth factor genes are excluded from this region. We have used dual colour FISH to determine the order of these cosmids, the order of the known genes mapped to 5q23-33 and the relationship of these genes to the critical region. To date, mutations of these genes in leukaemia cells have not been identified. The clinical features of myeloid diseases associated with a del(5q) are variable (RA 5q- syndrome v. AML); thus, once the involved gene is identified, it will be important to determine whether the same gene is involved in both types of myeloid disorders.

Acute Disease↗
PubMed2005

FGF7-like gene is associated with pericentric inversion of chromosome 9, and FGF7 is involved in the development of ovarian cancer.

Pericentric inversion of chromosome 9 is a common chromosomal aberration that may be involved in the pathogenesis of several types of cancer. Screening for structural balanced chromosomal aberrations in 58 patients with ovarian carcinoma found a patient with inv(9)(p11;q13) who had repeated spontaneous abortions. To define the breakpoint at the 9p11 region, the human 9p11-specific CEPH-YAC library was first screened with fluorescence in situ hybridization (FISH) analysis, resulting in isolation of the YAC clones 961d9 and 954b9 spanning the breakpoint. Next, screening with FISH analysis of the cosmid library constructed from 961D9 isolated 3 cosmid clones that included the breakpoint. DNA sequence analysis showed that the cosmid clones spanned the 57.7-kb sequence, which contained the FGF7 [keratinocyte growth factor (KGF)]-like gene including exons 2 and 3. FISH analysis showed that the 57.7-kb sequence was duplicated from the 9p11 region to the 9q13 region on the aberrant chromosome 9. Southern blot analysis showed multiple FGF7-like genes in the 9p11 region which were also duplicated to the 9q13 region on the aberrant chromosome 9. Because the FGF7-like genes are located at 9p11 and 9q13, our results are consistent with the hypothesis that the FGF7-like genes at 9p11 and 9p13 initiate the pericentric inversion of chromosome 9. Analysis of surgical specimens of ovarian cancer with the reverse transcription-polymerase chain reaction and immunohistochemical staining showed overexpression of the FGF7 gene in 4 of 9 stage I or II cases and in 10 of 11 stage III or IV cases. These findings suggest that FGF7 plays a significant role in the development of ovarian cancer.

Abortion, Spontaneous↗
PubMed2003

[Establishment of gene transduction system in geldanamycin producer - Streptomyces hygroscopicus 17997 and its application for gene disruption experiment].

Streptomyces hygroscopicus 17997 produces the antiviral and antitumor ansamycin antibiotic, geldanamycin. Studies on geldanamycin biosynthetic pathway will provide good tools for genetic manipulation of the antibiotic-producing strain to improve the productivity or to facilitate making novel geldanamycin analogs. The structural similarities between geldanamycin and ansamycins such as rifamycin or ansatrienin suggest that both geldanamycin and ansamycins has a closely related pathways of biosynthesis and that biosynthetic system for geldanamycin is similar to the one of type I polyketide synthase (PKS) enzyme system. To explore the possible PKS genes involved in geldanamycin biosynthesis, the degenerate primers were designed according to the conserved sequence of KS-AT region from erythromycin and oleandomycin type I PKS genes. Cosmids containing multiple PKS genes (pCGBK2,4,6,10,11,18) were obtained by hybridization with the PCR products, which were amplified from S. hygroscopisus 17997 genomic DNA. The designed primers above were used for PCR. Development of a Streptomyces temperate phage phiC31-derivative KC515( tsrR) transduction system was carried out for identification of cosmids containing the PKS gene related to biosynthesis of geldanamycin. Several factors, mainly the Ca2+ and Mg + concentrations in different culture media affecting the frequency of gene transfection, were optimized .Transfection efficiency could reach up to 10(3) /microg DNA on YMG medium supplemented with 10mmol/L MgSO4. Reversely, the transfection efficiency decreased when YMG medium was supplemented with 30mmol/L MgSO4. Gene transfection system based on the integration-defective phage KC515 had been established for S. hygroscopicus17997. Recombinant phages (ph111, 258, 287, 116, 105) were constructed by insertion of the homologous to PKS gene fragments into the KC515 phage vector. Gene disruption experiments were performed by transduction of recombinant phages into S. hygroscopicus 17997 genome, and disruption of geldanamycin production was observed as a result of homologous recombination between the cloned insert in recombinant phage and the S. hygroscopicus 17997 genome by integration. Thiostrepton resistant transductants were selected and integration event was analyzed by Southern hybridization. The fermentation broth extracts from five resistant transductants were analyzed by TLC and HPLC. The results showed that only G16 mutant failed to produce geldanamycin. This result showed that the integration of the insert DNA fragment in recombinant phage phl6 into the chromosome of S. hygroscopicus disrupted the expression of the geldanamycin biosynthetic genes. The original cosmid pCGBK10 containing this cloned insert was predicted to encode PKS genes in the geldanamycin biosynthesis. This study laid the foundation for cloning the PKS genes involved in geldanamycin biosynthetic gene cluster from S. hygroscopicus 17997.

Alcohol Oxidoreductases↗
PubMed2003

[Importance of five genes presented in Xenorhabdus nematophilus BP toxin gene cluster to its insecticidal activity].

Importance of five genes, named as xptA1, xptD1, xptB1, xptC1 and xptA2 presented in the toxin gene cluster of X. nematophilus BP strain, to its insecticidal activity against the neonate of Helicorvepa armigera was examined. This was achieved by analyzing and comparing the presence or absence of these five genes in and the insecticidal activity of each of the five clones screened from genomic cosmid library of X. nematophilus BP by in situ hybridization and another three subclones constructed from the enzyme-digested plasmid DNA of one of the insecticidal cosmid clones. The insecticidal activity of the clone or subclone was estimated by the 50% lethal concentration (LC50) of the neonate of H. armigera feed with the mixture of artificial diet and the cells of the clone or subclone examined. The presence or absence of each of the five genes in the clone or subclone was determined by the results of PCR amplification of the whole or the two ends of the targeted gene. The results indicated that: 1 the presence of xptC1 and xptA2 was critical for the full insecticidal activity of the toxin gene cluster while absence of xptD1 and/or xptA1 had little effect on the insecticidal activity against the neonate of H. armigera; 2. mixing cosmid clone XnBP76 and subclone Sub20k, which had a gene structure of (xptA1+, xptD1+, xptB1+, xptC1+ and xptA2-) and (xptA1-, xptD1-, xptB1-, xptC1- and xptA2+), respectively, did not achieve the full insecticidal activity. The functions of these five genes in the insecticidal process were discussed briefly.

Animals↗
PubMed1989

Penicillinase-type of beta-lactamase responsible for the ampicillin resistance in Escherichia coli NTUH 9501-1.

beta-Lactamases which hydrolyze the amide bonds of beta-lactam rings of penicillins and cephalosporins are widely distributed among microorganisms and play an important role in microbial resistance to beta-lactam antibiotics. These enzymes have been classified into penicillinase-type and cephalosporinase-type on the basis of their substrate specificity. Several clinical isolates of Escherichia coli from National Taiwan University Hospital (NTUH) were shown to be ampicillin-resistant and found to contain the penicillinase-type of beta-lactamase. Escherichia coli NTUH 9501-1 was chosen for further genetic analysis by recombinant DNA technology. DNAs from NTUH 9501-1 were isolated and digested with Pst I. The cellular DNA fragments were then joined with the vector DNA fragments derived from pHC 79 cosmid by Pst I digestion and followed by calf intestine alkaline phosphatase treatment. The recombinant cosmid DNAs were transfected and propagated in the wild type of E. coli DH 5. The transduced cells were selected on the basis of growth on LB plates containing ampicillin. The recombinant cosmid DNAs were re-isolated from the transductant cells and digested with Pst I. The cellular DNA fragments isolated by gel electrophoresis were able to transform DH 5 (amp(s)) to amp(r) cells. The results suggested that transposon-like DNA sequences coding for the ampicillinase-type of beta-lactamases were responsible for the penicillin resistance in E. coli NTUH 9501-1.

Ampicillin Resistance↗
PubMed1989

Molecular analysis of the rat MHC. II. Isolation of genes that map to the RT1.E-grc region.

An initial mapping analysis of growth and reproduction complex (grc) and grc+ genomic DNA identified several restriction fragment length polymorphisms specific for the grc region of the MHC. To analyze further the genomic organization and structure of the grc, a cosmid library was constructed from a grc+-bearing strain (R21). One cosmid cluster, encompassing 41.4 kb of DNA, contained four, or possibly five, class I genes that mapped to the RT1.E-grc region Two unique non-class I fragments were isolated from certain cosmids within this cluster. These fragments were hybridized to genomic DNA derived from five rat strains (BIL/2, R18, R21, R22, and BIL/1), and the results showed that grc-bearing rats have a deletion of at least 3.1 kb of DNA in the region immediately adjacent to the MHC. The loss of the genes in this region is probably the cause of the growth and reproductive defects in these animals and probably also of their increased susceptibility to chemical carcinogens.

Animals↗