OBJECTIVETo study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).

METHODSDNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.

RESULTSThe rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.

CONCLUSIONSACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.

Chromosomes ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; pathology ; Humans ; Loss of Heterozygosity ; Precancerous Conditions

Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder.
Articulation Disorders ; genetics ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 6 ; Forkhead Transcription Factors ; genetics ; Genetic Predisposition to Disease ; Humans

OBJECTIVETo explore the value of fluorescence in situ hybridization (FISH) and multiplex fluorescence in situ hybridization (M-FISH) techniques in the detection of genetic changes in chronic myeloid leukemia (CML) with variant Philadelphia translocation (vPh).

METHODSCytogenetic preparations from 10 CML patients with vPh confirmed by R banding were assayed with dual color dual fusion FISH technique. If only one fusion signal was detected in interphase cells, metaphase cells were observed to determine if there were derivative chromosome 9[der (9)] deletions. Meanwhile, the same cytogenetic preparations were assayed with M-FISH technique.

RESULTSOf the 10 CML patients with vPh, 5 were detected with der (9) deletions by FISH technique. M-FISH technique revealed that besides the chromosome 22, chromosomes 1, 3, 5, 6, 8, 10, 11 and 17 were also involved in the vPh. M-FISH technique also detected the abnormalities which were not found with conventional cytogenetics (CC), including two never reported abnormalities.

CONCLUSIONThe combination of CC, FISH and M-FISH technique could refine the genetic diagnosis of CML with vPh.

Adult ; Aged ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 10 ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Translocation, Genetic ; genetics ; Young Adult

OBJECTIVETo perform genetic analysis of a complex chromosome rearrangement (CCR) 46,XY, t(3;11)(q27; q13), ins(11;3)(q13;p26p13) in an azoospermic man.

METHODSPeripheral blood lymphocytes we re obtained for karyotyping, and metaphases were studied by multicolor fluorescence in situ hybridization procedure, Y chromosomal microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction.

RESULTSThe case was a complex chromosomal translocation between chromosomes 3 and 11 with four breakpoints, and accompanied with a band of chromosome 3 inserting into chromosome 11. No Y-chromosome microdeletions were identified at 6 STS sequences of the AZF loci.

CONCLUSIONCCR can have a significant impact on male fertility. Molecular cytogenetic techniques may contribute to improving and personalizing reproductive counseling.

Adult ; Azoospermia ; genetics ; Chromosome Breakage ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, X ; Chromosomes, Human, Y ; DNA ; analysis ; Humans ; Karyotyping ; Male ; Translocation, Genetic

Carcinoma in Situ ; genetics ; Carcinoma, Transitional Cell ; genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 17 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Urinary Bladder Neoplasms ; genetics

OBJECTIVETo characterize the profile of chromosomal imbalances of esophageal squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan province.

METHODSComparative genomic hybridization (CGH) was used to examine 52 cases of primary SCC of esophagus.

RESULTSGains in part or in whole of chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q were all significantly correlated with pathologic staging (P < 0.05). Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P < 0.05).

CONCLUSIONThese observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and 20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC-related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q are the genetic aberrations critical for the development of esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are considered later events associated with tumor progression and are thought to confer metastatic potential to esophageal carcinoma. Furthermore, nodal and distant organ metastases involve different genes.

Carcinoma, Squamous Cell ; genetics ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Esophageal Neoplasms ; genetics ; Gene Amplification ; Humans ; Lymphatic Metastasis ; Neoplasm Metastasis ; genetics ; Neoplasm Staging ; Nucleic Acid Hybridization

OBJECTIVEThe aim of this study was to characterize the profile of chromosomal imbalances of alveolar rhabdomyosarcoma (ARMS).

METHODSOne-step RT-PCR was used to detect the expression of PAX3-FKHR and PAX7-FKHR fusion transcripts in 10 cases of alveolar rhabdomyosarcoma and in an ARMS cell line. Comparative genomic hybridization (CGH) was used to investigate the genomic imbalances in these cases. It was analyzed according to the histological type, pathologic grading, clinical staging, gender and age, respectively.

RESULTSThe 10 patients with alveolar rhabdomyosarcoma showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome arms of ARMS were 12q, 2p, 6p, 6q, 10q, 2q, 4q, 15q, 1p, 9q, 14q and 18q (> or = 30.0%), and the frequently lost chromosome arms of ARMS were 3p, 6p, 20q and 21q (> 30.0%). (2) The frequently gained chromosome arm translocation associated with ARMS were 12q, 10q, 2p, 2q, 6p, 6q, 1p, 4q, 8q, 11q, 14q and 15q (> 30.0%). The frequently lost chromosome arms were 3p, 5q, 6p, 1q, 8p, 11p, 20q and 21q (> 30.0%). (3) There were no correlation between chromosome changes and histological type, pathologic grade, clinical stage, gender and age, respectively.

CONCLUSIONThese observations suggest that: (1) 12q, 2p, 6p, 6q, 10q, 2q, 4q, 15q, 1p, 9q, 14q, 18q gain and 3p, 6p, 20q, 21q loss may correlated with ARMS-related carcinogenesis; (2) 12q gain may be correlated with translocation.

Adolescent ; Adult ; Aged ; Cell Line, Tumor ; Child ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 12 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Humans ; Infant ; Male ; Neoplasm Staging ; Oncogene Proteins, Fusion ; metabolism ; PAX7 Transcription Factor ; metabolism ; Rhabdomyosarcoma, Alveolar ; genetics ; metabolism ; pathology ; Young Adult

OBJECTIVETo characterize the profiles of chromosome imbalance in esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the high incidence area in Henan.

METHODSChromosomal aberrations of 37 samples of SCC and 30 GCA were analyzed by comparative genomic hybridization comparative genomic hybridization (CGH).

RESULTSIt was found that the most frequently detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and 7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%), and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p (57%), and followed by 19p, 1p and 4p.

CONCLUSIONThe present findings demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance in GCA, which provide important theoretic information for identifying and cloning novel SCC/GCA-related genes.

Adenocarcinoma ; genetics ; Carcinoma, Squamous Cell ; epidemiology ; genetics ; Cardia ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 20 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; genetics ; Esophageal Neoplasms ; epidemiology ; genetics ; Gene Amplification ; Gene Deletion ; Humans ; Nucleic Acid Hybridization ; methods ; Stomach Neoplasms ; epidemiology ; genetics

OBJECTIVETo search the susceptibility genes of gallstone disease in Chinese population.

METHODSA genome wide scan was performed in twelve families with gallstone disease using fluorescence-labeled microsatellite markers. Genehunter and Batchlink of Linkage package were used for non- parameter and parameter linkage analysis to search the linkage loci on chromosomes.

RESULTSFour loci of D3S1266, D4S406, D9S1682 and D11S902 showed suggestive evidence for linkage. nonparametric linkage analysis (NPL)-score of D4S406 and D9S1682 was 1.77 (P = 0.05) and 1.92 (P = 0.04) respectively. The corresponding logarithm of the odds ratio (LOD)-score of D3S1266, D9S1682 were 1.35 and 2.07, and showed a rise of LOD-score from 1.35 to 2.71, 2.07 to 2.40 respectively when families with later-found patients or with higher triglyceride level were analyzed alone. Transmitted disequilibrium test of D11S902 showed a P-value of 0.0027.

CONCLUSIONSChromosome 3, 4, 9 and 11 may contain genes involved in gallstone disease in Chinese population, and chromosome 3, 9 may hide genes that are liked to gallstone disease in families with later-found patients or with higher triglyceride concentration.

Age Factors ; Asian Continental Ancestry Group ; Body Mass Index ; Cholecystolithiasis ; ethnology ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Female ; Genetic Linkage ; Genetic Predisposition to Disease ; Humans ; Male ; Microsatellite Repeats ; Pedigree

OBJECTIVETo get the genotype and allele frequency distributions of 8 short tandem repeat (STR) loci on chromosome 3p (D3S1297, D3S1489, D3S1266, D3S1568, D3S1289, D3S1300, D3S1285 and D3S3681) in Chinese Han population in Hunan area.

METHODSBlood samples were collected from the random Han individuals in Hunan and the whole genomic DNA was extracted. STR loci were amplified by multiplex-PCR technique and genotyped by ABI 377 sequencer.

RESULTSNinety-one alleles were detected, with frequencies ranging from 0.002 to 0.431, and these alleles constituted 312 genotypes. All the 8 loci met Hardy-Weinberg equilibrium. The statistical analysis of 8 STR loci showed the heterozygosity (H) >or= 0.729, the discrimination power (DP) >or= 0.725, the probabilities of paternity exclusion (PPE) >or= 0.596, and the polymorphic information content (PIC >or= 0.682). The result indicated that there was a significant difference between Han ethnic group and the white and the black.

CONCLUSIONThese results could serve as valuable data to enrich the Chinese genetic database and play an important role in Chinese population genetic and forensic medical application.

Adult ; Alleles ; China ; Chromosomes, Human, Pair 3 ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic