Siblings with opposite chromosome constitutions,dup(2q)/del(7q) and del(2q)/dup(7q)

Chromosome 7q36 microdeletion syndrome is a rare genomic disorder characterized by underdevelopment of the brain, microcephaly, anomalies of the sex organs, and language problems. Developmental delay, intellectual disability, autistic spectrum disorders, BDMR syndrome, and unusual facial morphology are the key features of the chromosome 2q37 microdeletion syndrome. A genetic screening for two brothers with global developmental delay using high-resolution chromosomal analysis and subtelomeric multiplex ligation-dependent probe amplification revealed subtelomeric rearrangements on the same sites of 2q37.2 and 7q35, with reversed deletion and duplication. Both of them showed dysmorphic facial features, severe disability of physical and intellectual development, and abnormal genitalia with differential abnormalities in their phenotypes. The family did not have abnormal genetic phenotypes. According to the genetic analysis of their parents, adjacent-1 segregation from their mother's was suggested as a mechanism of their gene mutation. By comparing the phenotypes of our patients with previous reports on similar patients, we tried to obtain the information of related genes and their chromosomal locations.     

Variance‐Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q

To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome‐wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ～75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores ≥1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine‐mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31‐q42 and 11q14‐q24.     

Evidence for linkage of migraine in Rolandic epilepsy to known 1q23 FHM2 and novel 17q22 genetic loci

Migraine headaches are a common comorbidity in Rolandic epilepsy (RE) and familial aggregation of migraine in RE families suggests a genetic basis not mediated by seizures. We performed a genome‐wide linkage analysis of the migraine phenotype in 38 families with RE to localize potential genetic contribution, with a follow‐up in an additional 21 families at linked loci. We used two‐point and multipoint LOD (logarithm of the odds) score methods for linkage, maximized over genetic models. We found evidence of linkage to migraine at chromosome 17q12‐22 [multipoint HLOD (heterogeneity LOD) 4.40, recessive, 99% penetrance], replicated in the second dataset (HLOD 2.61), and suggestive evidence at 1q23.1‐23.2, centering over the FHM2 locus (two‐point LOD 3.00 and MP HLOD 2.52). Sanger sequencing in 14 migraine‐affected individuals found no coding mutations in the FHM2 gene ATP1A2. There was no evidence of pleiotropy for migraine and either reading or speech disorder, or the electroencephalographic endophenotype of RE when the affected definition was redefined as those with migraine or the comorbid phenotype, and pedigrees were reanalyzed for linkage. In summary, we report a novel migraine susceptibility locus at 17q12‐22, and a second locus that may contribute to migraine in the general population at 1q23.1‐23.2. Comorbid migraine in RE appears genetically influenced, but we did not obtain evidence that the identified susceptibility loci are consistent with pleiotropic effects on other comorbidities in RE. Loci identified here should be fine‐mapped in individuals from RE families with migraine, and prioritized for analysis in other types of epilepsy‐associated migraine.     

Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13

Four human homeo box-containing cDNAs isolated from mRNA of an SV40-transformed human fibroblast cell line have been regionally localized on the human gene map. One cDNA clone, c10, was found to be nearly identical to the previously mapped Hox-2.1 gene at 17q21. A second cDNA clone, c1, which is 87% homologous to Hox-2.2 at the nucleotide level but is distinct from Hox-2.1 and Hox-2.2, also maps to this region of human chromosome 17 and is probably another member of the Hox-2 cluster of homeo box-containing genes. The third cDNA clone, c8, in which the homeo box is approximately 84% homologous to the mouse Hox-1.1 homeo box region on mouse chromosome 6, maps to chromosome region 12q12----12q13, a region that is involved in chromosome abnormalities in human seminomas and teratomas. The fourth cDNA clone, c13, whose homeo box is approximately 73% homologous to the Hox-2.2 homeo box sequence, is located at chromosome region 2q31----q37. The human homeo box-containing cluster of genes at chromosome region 17q21 is the human cognate of the mouse homeo box-containing gene cluster on mouse chromosome 11. Other mouse homeo box-containing genes of the Antennapedia class (class I) map to mouse chromosomes 6 (Hox-1, proximal to the IgK locus) and 15 (Hox-3). A mouse gene, En-1, with an engrailed-like homeo box (class II) and flanking region maps to mouse chromosome 1 (near the dominant hemimelia gene). Neither of the class I homeo box-containing genes--c8 and c13--maps to a region of obvious homology to chromosomal positions of the presently known mouse homeo box-containing genes.     

Partial trisomy 2q and familial translocation t(2;12)(q31;q24)

Summary Report is given of a boy with trisomy of the distal part of the long arm of chromosome 2 (q31ter) due to a balanced 2/12 translocation in the mother: 46,XX,t(2;12) (q31;q24). Other phenotypically normal carriers of this balanced translocation are the patients sister and grandfather. The patient shows a variety of dysplastic signs mainly of the face.     

Mosaic and non-mosaic trisomy 15q2

Two unrelated patients are presented. In the first mosaicism with normal cells and cells trisomic for the distal long arm (q2) of chromosome 15 was found. The 15q2 trisomy was due to a chromosome 14, to the long arm of which an extra 15q2 region was attached (14pter----14q32::15q22----15qter). In the second trisomy 15q2 was present as a consequence of a balanced t(7;15)(p22;q15) translocation in the mother.     

Genome-wide association study identifies 7q11.22 and 7q36.3 associated with noise-induced hearing loss among Chinese population

Noise-induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome-wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls. We identified that four candidate pathways were nominally significantly associated with NIHL, including the Erbb, Wnt, hedgehog and intraflagellar transport pathways. In addition, two novel index single-nucleotide polymorphisms, rs35075890 in the intron of AUTS2 gene at 7q11.22 (combined P = 1.3 × 10⁻⁶) and rs10081191 in the intron of PTPRN2 gene at 7q36.3 (combined P = 2.1 × 10⁻⁶), were significantly associated with NIHL. Furthermore, the expression quantitative trait loci analyses revealed that in brain tissues, the genotypes of rs35075890 are significantly associated with the expression levels of AUTS2, and the genotypes of rs10081191 are significantly associated with the expressions of PTPRN2 and WDR60. In conclusion, our findings highlight two novel loci at 7q11.22 and 7q36.3 conferring susceptibility to NIHL.     

Partial trisomy 14q and familial translocation (2;14) (q12;q13).

A female patient with moderate psychomotor retardation, minor anomalies and proximal trisomy 14q due to segregation of a maternal translocation is reported.     

Prenatal diagnosis of ring chromosome 2 with lissencephaly and 2p25.3 and 2q37.3 microdeletions detected using array comparative genomic hybridization

We present rapid aneuploidy diagnosis of ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions by aCGH using uncultured amniocytes in a fetus with IUGR, microcephaly, lissencephaly and ambiguous external genitalia. Our case adds lissencephaly to the list of CNS abnormalities in ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions. We discuss the consequence of haploinsufficiency of HDAC4, KIF1A, PASK, HDLBP, FRAP2 and D2HGDH on 2q37.3, and haploinsufficiency of MYT1L, SNTG2 and TPO on 2p25.3 in this case.     

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 2q and familial translocation t(2;18)(q31;p11)

Summary This report describes a malformed infant with distal 2q trisomy/ distal 18p monosomy due to adjacent segregation of a familial t(2;18). The rearrangement was present in four generations, and linkage studies were performed.     

Guinea pig (Cavio cambayo) 5S rRNA genes map to 7q2, 20q2 and 30q2 shown by an R-banded karyotype with PNA-FISH

A karyotype for the guinea pig (Cavio cambayo) is proposed based on an R-banding pattern. R-bands were obtained by BrdU incorporation into the cells followed by a combined DAPI and propidium iodide staining of the fixed metaphase spreads. In situ hybridization was performed with two biotinylated 18-mer PNA (peptide nucleic acid) probes complementary to sequences within the 5S rRNA gene. The 5S rRNA gene repeats map to chromosomes 7q2. 20q2 and 30q2, respectively.     

CXCL2/CXCR2 axis induces cancer stem cell characteristics in CPT-11-resistant LoVo colon cancer cells via Gαi-2 and Gαq/11

Cancer stem cells (CSCs) exist in colon cancer and exhibit characteristics of stem cells which are due to lineages of tissues where they arise. Epithelial to mesenchymal transition (EMT)-undergoing cancer cells display CSC properties and therapeutic resistance. Cancer and stromal cells comprise of a tumor microenvironment. One way the two populations communicate with each other is to secret CXC ligands (CXCLs). CXCLs are capable of causing chemotaxis of specific types of stromal cells and control angiogenesis. Double immunofluorescence, western blot analysis, and colony-formation assay were carried out to compare parental and CPT-11-resistant LoVo cells. CPT-11-R LoVo colon cancer cells showed increased expression of CXCL1, CXCL2, CXCL3, and CXCL8. They displayed significantly increased intracellular protein levels of CXCL2 and CXCR2. CPT-11-R LoVo cells showed significantly elevated expression in aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 24 (CD24), cluster of differentiation 44 (CD44), and epithelial cell adhesion molecule (EpCAM). CXCL2 knockdown by short hairpin RNA resulted in reduced expression of CSC proteins, cyclins, EMT markers, G proteins, and matrix metalloproteinases (MMPs). Finally, Gαi-2 was found to promote expression of CSC genes and tumorigenesis which were more apparent in the resistant cells. In addition, Gαq/11 showed a similar pattern with exceptions of EpCAM and MMP9. Therefore, CXCL2–CXCR2 axis mediates through Gαi-2 and Gαq/11 to promote tumorigenesis and contributes to CSC properties of CPT-11-R LoVo cells.