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

Split hand split foot malformation (SHFM) is a human developmental disorder characterized by a deep median cleft in the hands and feet, missing digits, and fusion of the remaining digits. The disease itself is considered to be very rare, affecting one out of 90,000 newborn babies. SHFM is genetically heterogeneous. To date, five SHFM loci have been mapped, to chromosome 2, 3, 7, 10 and X, respectively. We experienced a case of SHFM in a male neonate who had lobster-claw deformities of the hands and feet. The karyotype of his chromosome was 46,XY,inv (9) (p12q13). We report the case with the review of the associated literatures.
Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 9* ; Congenital Abnormalities ; Foot* ; Hand* ; Human Development ; Humans ; Infant, Newborn ; Karyotype ; Male

This study was purposed to investigate the acute myeloid leukemia with complex karyotype t(2;21;8)(p12;q22;q22) (AML-M(2)) by using morphologic, immunologic, cytogenetic and molecular biologic classification technique (MICM) and to analyze the MICM characteristics of AML-M(2) and their diagnostic significance. The FAB typing of bone marrow cells (BMCs) was performed by Wright-Giemsa staining and histochemical staining of BM smears; the immunophenotype of leukemic cells was detected by flow cytometry; the karyotypes of chromosome samples prepared by short-term (48 hours) conventional culture of fresh BMCs were analyzed by RHG banding technique; the FISH signaling in mitotic metaphase was determined by dual color and dual fusion AML/ETO probe and chromosome painting probe, and was compared with results of conventional cytogenetic assay; the AML/ETO fusion transcripts were detected by nested RT-PCR. The results indicated that the bone marrow smears of case 1 showed extremely hyperplasia with myeloblasts in which a ratio of eosinophilic granulocytes and monocytes increased. Case 2 accorded with AML-M(2b) in which abnormal increase of myelocytes mainly appeared. The complex karyotype t(2;21;8)(p12;q22;q22) was detected by cytogenetic analysis combined with FISH in both two cases and AML1/ETO fusion transcripts were found by RT-PCR as well. The immunophenotype assay showed high co-expression of CD34 and HLA-DR accompanied with CD19 and CD56 expressions. It is concluded that application of MICM has an important significance for correct diagnostic typing of AML-M2 with complex karyotype variant of t(8; 21)(p12;q22;q22).
Adult ; Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Female ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged

OBJECTIVE: To carry out cyto- and molecular genetic testing for a child featuring facial dysmorphism and attention deficit and hyperactive disorder. METHODS: The child was subjected to routine peripheral blood lymphocyte chromosomal karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) analyses. RESULTS: The child's facial dysmorphism included low-set ears, curly ear auricle, protuberance of eyebrow arch, nostril notch, short and flat philtrum and thin upper lip. SNP-array revealed that he has carried a 4.883 Mb deletion at 2q37. His chromosomal karyotype was ultimately determined as 45, XY, der(2;21) (2pter→ 2q37.3::21p13→ 21p10::20p10→ 20pter), der(20) (21qter→ 21q10::20q10→ 20qter). CONCLUSION A rare case of 2q37 deletion syndrome involving three chromosomes was discovered. Combined use of various cyto- and molecular genetic techniques is crucial for the diagnosis of chromosomal abnormalities with complex structures.
Child ; Chromosome Deletion ; Chromosomes ; Chromosomes, Human, Pair 2 ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Translocation, Genetic

OBJECTIVE: To identify the Epstein-Barr virus (EBV) chromosomal integration sites in Raji cells. METHODS: EBV DNA was detected by Southern hybridization, and the viral chromosomal integration sites were identified using G banding and fluorescence in situ hybridization (FISH). RESULTS: BamHI-digested genomic DNA from Raji cells was hybridized with (32)P-labeled probe-1 (EBV genome 13,232 approximately 16,189) and Probe-2 (EBV genome 5 approximately 3,271), which generated 4 and 10, 23 kb positive bands respectively. The viral integration sites included 1p, 1q, 2q, 3p, 3q, 4 q, 5q, 6q, 7p, 7q, 9q,11p, 14 q, and 15q,and chromosomal bands 4 q, 2q, 1q and 7q were viral integration sites with high frequencies. Among the 33 signals counted, 7, 4, 4,and 4 signals were at the site 4 q, 2q, 1q, and 7q respectively, and 64% of the total signals were found in these 4 chromosomal bands. No viral integration occurred in chromosomes 16 approximately 22 or the sex chromosomes (X, Y). CONCLUSION This study firstly identifies the EBV integration sites in Raji cells using G banding and FISH. There are some viral integration sites with high frequencies in Raji cells, and EBV integrates into Raji cell genomes non-randomly.
Burkitt Lymphoma ; genetics ; pathology ; virology ; Cell Line, Tumor ; Chromosomes, Human, Pair 1 ; virology ; Chromosomes, Human, Pair 2 ; virology ; Chromosomes, Human, Pair 4 ; virology ; DNA, Viral ; genetics ; Genome, Viral ; Herpesvirus 4, Human ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Virus Integration ; genetics

OBJECTIVETo explore whether chromosomal microdeletions have a role in the pathogenesis of unexplained mental retardation (MR) and the value of fluorescence in situ hybridization (FISH) in the detection of microdeletions in MR.

METHODSSelection of patients was based on the following criteria: (1) MR with two or more of the following: dysmorphic features, prenatal growth retardation, postnatal growth abnormalities, a suggestive family history; (2) Chromosome karyotype at the level >450 bands was normal; (3) Exclusion of other identified genetic or environmental diagnosis. FISH was carried out with specific DNA probe to 47 undiagnosed MR to identify interstitial microdeletions and further screen the integrity chromosome subtelomere.

RESULTSSix cases were analyzed by FISH for special interstitial microdeletions and anomaly was found in one case with 7q11.23 deletion. Subtelomeric FISH analyses were performed in 46 patients, and two cases with a deletion of subtelomeric region of chromosome 6q and 2q respectively were identified.

CONCLUSIONChromosome microdeletions are supposed to be a significant cause of idiopathic MR, once recognizable syndromes have been excluded, FISH analyses for interstitial microdeletions and subtelomeric rearrangements are warranted in children with unexplained MR.

Chromosome Deletion ; Chromosomes, Human, Pair 2 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Genetic Predisposition to Disease ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics

Prader-Willi syndrome is a disease of chromosome 15, which is characterized by severe hypotonia and feeding difficulty in neonates, followed by development of obesity, mental retardation, and hypogonadism. Approximately 70% of the patients have a paternal deletion on chromosome 15q11-13, which is mainly a microdeletion, and a large deletion due to an unbalanced structural translocation of the proximal long arm of chromosome 15 to several other chromosomes is rarely found. We encountered a neonatal case with Prader-Willi syndrome who had sustained hypotonia and feeding difficulty. On high-resolution chromosome analysis, deletion of the short arm and the proximal part of the long arm of chromosome 15, with unbalanced translocation of the remaining part of chromosome 15(q13-qter) to the terminal part q37 of chromosome 2, was shown to be <45,XX, -15, der(2) t(2;15) (q37:q13)>. Through FISH (Fluorescence in situ hybridization) and methylation-specific DNA PCR, we confirmed the deleted q11-13 was derived from the father.
Arm ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 2* ; DNA ; Fathers ; Humans ; Hypogonadism ; Infant, Newborn ; Intellectual Disability ; Muscle Hypotonia ; Obesity ; Polymerase Chain Reaction ; Prader-Willi Syndrome*

OBJECTIVE: To investigate the genetic polymorphism of 15 short tandem repeat(STR)loci on chromosome 2 and chromosome 11 in Shaanxi Han people in China. METHODS: Fluorescence-based gene scan technique was used to examine the genetic polymorphism of 15 STR loci in 175 unrelated individuals from Chinese Han population in Shannxi province. RESULTS: The number of alleles D2S335, D2S396, D2S338, D2S2382, D2S305, D2S151, D2S2368, D2S391,D11S912, D11S4090, D11S4147, D11S4190, D11S4149, D11S4126, and D11S4094 was 11,11,11,10,8,8,9,12 ,7,11,8,10,5,5, and 6. The distribution of allele frequencies of the 15 STR was consistent with Hard-Weinberg equilibrium (P > 0.05). Heterozygosity (H) value was 0.4216 to approximately 0.8517, the average power of discrimination (DP) was 0.6568 to approximately 0.9598, polymorphism information content (PIC) was 0.4078 to approximately 0.8366, and probability of paternity exclusion (EPP) was 0.3135 to approximately 0.8537. CONCLUSION The 15 STR loci have relatively high genetic polymorphism in Shaanxi Han population, which provides the genetic structure of Chinese Han groups, and is also useful in anthropology and forensic science.
Adult ; China ; ethnology ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 2 ; genetics ; Female ; Gene Frequency ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic

Immunoglobulin A nephropathy (IgAN), which can develop into end-stage renal disease, is the most common primary glomerulonephritis. The pathogenesis of IgAN is not clear. Many studies have confirmed that genetic susceptibility is associated with IgAN, and it belongs to polygenic disease. Some studies have found that IgAN is associated with chromosome 6q22-23, 2q36 by linkage analysis, and several candidate genes have been confirmed to be associated with IgAN, such as angiotensin converting enzyme, Fc fragment of IgA receptor, human leukocyte antigen. In recent years, as the progression of molecular genetics and the Human Genome Project, more attention has been paid to the role of genetic factors in the pathogenesis of IgAN.
Animals ; Chromosomes, Human, Pair 2 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Genetic Association Studies ; Genetic Linkage ; Genetic Predisposition to Disease ; genetics ; Glomerulonephritis ; complications ; Glomerulonephritis, IGA ; etiology ; genetics ; Humans

OBJECTIVETo report a case of acute myeloid leukemia (AML) with the insertion (8;21)(q22;q22.1q22.3). A 33-year-old Chinese woman was referred to our hospital. Hematologic data showed WBC 42.7 x 10(9)/L with monocytosis (monocyte counts 7.296 x 10(9)/L). Bone marrow aspirate was hypercellular with 4.5% monoblasts and 7.5% promonocytes. At first she was diagnosed with chronic myelomonocytic leukemia (CMML) according to the FAB criteria. Initially the patient received supportive care only, but her general condition rapidly became worse three months later. The monoblasts and promonocytes in the bone marrow rose to 20.5%. After two cycles of combined chemotherapy she obtained complete remission.

METHODSChromosome specimens were prepared by short-term culture of bone marrow cells. Karyotype analysis was carried out by R-banding technique. Three fluorescence in situ hybridization (FISH) analyses were performed using AML1-ETO dual color, dual fusion probe, whole chromosome painting 8 and 21 probes, and cen-8 and Tel 21qter probes, respectively. Reverse transcription polymerase chain reaction (RT-PCR) assay for detecting the AML1-ETO fusion transcript was also performed.

RESULTSConventional cytogenetic analysis showed a karyotype of 46,XX,ins(8;21) (q22;q22.1q22.3)[7]/46,XX[3]. FISH tests confirmed the insertion. RT-PCR analysis detected the AML1-ETO fusion transcript.

CONCLUSIONWe consider that this patient should be rediagnosed as acute myeloid leukemia according to the criteria proposed by World Health Organization (WHO) and that FISH and RT-PCR play an important role in verification of the ins(8;21).

Chromosome Banding ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 19 ; Chromosomes, Human, Pair 8 ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Leukemia, Myeloid ; genetics ; Translocation, Genetic