Co-inheritance of sickle cell trait and thalassemia mutations in South central iran.

BACKGROUND: We aimed to determine the incidence of co-inheritance as well as interaction of sickle cell trait (SCT) and α(thal)/ß(thal) mutations in south and south central of Iran. METHOD: We employed a PCR and restriction fragment length polymorphism techniques to confirm diagnosis of sickle cell trait. All subjects were screened for any α/ß -thalassemia mutations using a gap-polymerase chain reaction and amplification refractory mutations system. RESULTS: Our results showed combination of sickle cell trait and ß-globin mutation results in a severe clinical course of similar to sickle cell disease, while coinheritance of α-globin gene defects usually modulates the clinical course. A coexistence of sickle cell trait and α-globin gene mutation was the frequent genotype in overall samples (57. 5%). CONCLUSION: Sickle cell trait mainly co-inherits with α-globin gene mutation in the south and south central region of Iran. This combination modulates hematological indices and interferes with the SCT diagnosis.

Distribution of ß-Globin Gene Mutations in Thalassemia Minor Population of Kerman Province, Iran.

BACKGROUND: Mutations in ß-globin gene may result in ß-thalassemia major, which is one of the most common genetic disorders in Iran and some other countries. Knowing the beta-globin mutation spectrum improves the efficiency of prenatal diagnosis in the affected fetuses (major ß-thalassemia) of heterozygote couples. METHODS: Couples with high hemoglobin A(2) and low mean corpuscular volume were studied as suspicious of ß-thalassemia carriers in Genetic Laboratory of Afzalipour Hospital, Kerman, Iran. We used amplification refractory mutation system, reverse hybridization, and DNA sequencing to determine the spectrum of ß-globin gene mutation in the people who involved with ß-thalassemia minor in this province. RESULTS: Among the 266 subjects, 17 different types of mutation in ß-globin gene were identified. Three of the mutations account for 77.1% of the studied cases. IVSI-5(G> C) was the most frequent mutation (66.2%) followed by IVSII-I (G> A) (6%) and Fr 8-9 (+G) (4.9%). The less frequent mutations include: IVSI-6(T> C), codon 15 (G>A), codon 44 (-C), codon 39 (C>T), codon 8 (-AA), codon30 (G> C), IVSI-110 (G > A), codon 36-37 (-T), 619bp deletion, codon 5 (-CT), IVSI-25bp del, codon 41-42(-TTCT), IVSI-I (G> A), and ßnt30 (T>A) were accounted for 19.5%. Unknown alleles comprised 3.4% of the mutations. CONCLUSION: However, the frequencies of different mutations reported here are significantly different from those found in other part of the world and even other Iranian provinces. Reporting a number of these mutations in the neighboring countries such as Pakistan can be explained by gene flow phenomenon.

RAD51C (RAD51L2) is involved in maintaining centrosome number in mitosis.

The RAD51C (RAD51L2) protein is one out of five RAD51 paralogs and forms a complex that includes either XRCC2 or XRCC3. Both of these complexes may have important functions in homologous recombination (HR). Here, we confirm that the frequency of DNA double-strand break (DSB)-induced HR is reduced in the RAD51C deficient cell line CL-V4B, in agreement with a role for RAD51C in HR. We report that mitotic RAD51C deficient CL-V4B cells also have an increased number of centrosomes in mitosis resulting in aberrant mitotic spindles. These data suggest that the RAD51C protein is important in maintaining correct centrosome numbers and that the complexes including RAD51C and XRCC2 or XRCC3 may be of importance in maintaining correct centrosome numbers in mitosis. Increased centrosome numbers following a RAD51C defect indicates that this protein might be important in preventing aneuploidy, suggesting that it could be a potential tumour suppressor in mammals.