Disease relevance of TTTY3B

• Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene [1].
• The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C [2].
• RESULTS: Using FISH, we have identified patterns of DNA loss and gain of certain chromosome-specific centromeric markers in DCIS [3].
• METHODS: Fifty-one sectors characterized by low- and high-grade dysplasia and early cancer were microdissected from 34 adenomas, and isolated epithelial nuclei were subjected to hybridization with probes to the telomeric and centromeric regions of chromosome 1 [4].
• 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 [5].

Psychiatry related information on TTTY3B

• All five patients displayed the classical features of 3p- syndrome (mental retardation, growth retardation, microcephaly, ptosis and micrognathia) demonstrating that loss of sequences centromeric to D3S1317 is not required for expression of the characteristic 3p- syndrome phenotype [6].
• (GTG)(n) and other repetitive sequences generally showed a replication pattern similar to that of the bulk of DNA with slightly individual differences, whereas centromeric DNA repeats consistently replicated within a short time frame in late S phase [7].
• Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus [8].
• FISH analysis of metaphase chromosomes in a cohort of 33 girls with Rett syndrome (RTT) allowed us to detect eight girls with structurally different X chromosomes, one X chromosome with a large and another one with a small centromeric heterochromatin (so-called chromosomal heteromorphism) [9].

High impact information on TTTY3B

• C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability [10].
• PICH-positive threads connect sister kinetochores and are dependent on tension, sensitive to DNase, and exacerbated in response to premature loss of cohesins or inhibition of topoisomerase II, suggesting that they represent stretched centromeric chromatin [11].
• We propose that in vertebrates, a cleavage-independent pathway removes cohesin from chromosome arms during prophase, whereas a separin-dependent pathway cleaves centromeric cohesin at the metaphase-anaphase transition [12].
• Thus, we show M31 overexpression to have two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric [13].
• Together, our results suggest that the functional enhancer antagonizes gene silencing by preventing localization of a gene near centromeric heterochromatin [14].

Chemical compound and disease context of TTTY3B

• An in situ hybridization (ISH) study on paraffin sections of 13 malignant mesotheliomas was performed to detect numerical chromosomal aberrations with biotin-labelled DNA probes specific for the centromeric regions of chromosomes 1, 3, 6, 7, 11, and 17 [15].
• Formalin-fixed, paraffin-embedded sections from 28 cases of ductal carcinoma in situ (DCIS; 12 with coexisting invasive neoplasm) were analyzed for numerical alterations of chromosomes 7, 8, 16, and 17 by performing fluorescence in situ hybridization (FISH) using centromeric (alpha-satellite) probes [16].
• METHODS AND RESULTS: Chromosomal in-situ hybridization was performed on deparaffinized tissue sections from 20 Barrett's adenocarcinomas, 20 adenocarcinomas of the cardia and 20 adenocarcinomas of the antrum, with centromeric alpha satellite DNA probes specific for chromosomes 7, 8, 11, 17 and Y, labelled with digoxigenin [17].

Biological context of TTTY3B

• Furthermore, the orientation of these gene fragments on their truncated chromosomes reveal that the healed chromosome originally associated with centromeric elements is mitotically stable and maintained [18].
• To test the hypothesis that alpha-satellite DNA, the major centromeric satellite of primate chromosomes, is involved in centromere structure and/or function, human alpha-satellite DNA was introduced into African green monkey (AGM) cells [19].
• Padlock probes reveal single-nucleotide differences, parent of origin and in situ distribution of centromeric sequences in human chromosomes 13 and 21 [20].
• The relationship between the kinetochore and the centromeric heterochromatin that surrounds it is unknown [21].
• A characteristic arrangement of the repeat motifs in three separate spots, oriented transverse to the length axis of the metaphase chromosomes and bilaterally symmetric, indicates that only parts of the detected regions are involved in the centromeric region, joining the sister chromatids before anaphase [20].

Anatomical context of TTTY3B

• The chromosome-4 breakpoints are clustered in a 70-kb region centromeric to the fibroblast growth factor receptor 3 gene (FGFR3), the apparent dysregulated oncogene [22].
• The separation of V beta and C beta observed in somatic cell hybrids defined the orientation of the T cell receptor beta chain locus on chromosome 7 where the V beta genes are centromeric and the C beta genes are telomeric [23].
• The kinetochore is a proteinaceous structure that assembles onto centromeric DNA and mediates chromosome attachment to microtubules during mitosis [24].
• Pericentromeric targeting did not result from an interaction with the Mi-2 remodeling factor, as only a small percentage of Mi-2 localized to centromeric foci in 3T3 cells [25].
• Furthermore, the serologic studies of HLA-deletion mutant cell lines demonstrate that there are two HLA regions centromeric to HLA-B controlling expression of Ia-like molecules: a region toward HLA-B that controls expression of HLA-DR, and a region toward GLO that controls expression of SB [26].

Associations of TTTY3B with chemical compounds

• The C- and G-positive regions stained with distamycin A-DAPI, which is specific for the centromeric heterochromatin of chromosomes 1, 9, 15p, 16, and Y. DNA extracted from MeWo cells and digested with the restriction enzymes KpnL or Sau3A exhibited marked amplification of a 1.8-kilobase fragment [27].
• These two sets encompass the 340 kb separating the C2 and tumour necrosis factor (TNF) alpha and beta genes, except for a 22 kb gap 108 kb centromeric to the TNF alpha gene [28].
• The centromeric regions of the variant chromosome 6 and its homologue are not significantly elongated by adding 5-azacytidine to culture [29].
• 5. However, as the p57KIP2 gene is 500 kb centromeric to the gene encoding insulin-like growth factor 2, it is likely to be part of a large domain containing other imprinted genes [30].
• Deletion of the Dicer (dcr1+) gene caused slow growth, sensitivity to thiabendazole, lagging chromosomes during anaphase, and abrogated silencing of centromeric repeats [31].

Analytical, diagnostic and therapeutic context of TTTY3B

• Similarly, the DR alpha-chain gene has been mapped to the short arm of chromosome 6 centromeric to the HLA-A, -B and -C loci by in situ hybridization experiments [32].
• Here we report a high-resolution physical map of the euchromatic, centromeric and heterochromatic regions of the NRY and its construction by unusual methods, including genomic clone subtraction and dissection of sequence family variants [33].
• Despite the complete absence of normal centromeric alpha-satellite DNA, human neocentromeres are able to form a primary constriction and assemble a functional kinetochore [34].
• Southern blot analysis of NotI-digested, pulsed-field gel electrophoresis-separated DNA indicates the gelsolin gene is greater than or equal to 40 kb centromeric to ABL [35].
• As measured by pulsed-field gel electrophoresis, the total D16Z2 array spans approximately 1,400-2,000 kb of centromeric DNA [36].

References