Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; Krefting Research Centre, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.
Mutat Res. 2020 May-Dec;821:111708. doi: 10.1016/j.mrfmmm.2020.111708. Epub 2020 May 23.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for Cystic Fibrosis (CF) disease. Since the distribution of polymorphisms varies among populations, a comparison between the frequency of CFTR polymorphisms in patients and healthy population may further identify their role in CF disease. The results obtained from this research may facilitate the prediction of disease phenotype in prenatal diagnosis or newborn screening program as well as determine the possible associations between haplotypes and specific mutations.
Blood samples collected from 27 unrelated West Iranian families contain at least one CF patient and 55 control families with no history of CF. Samples were analyzed for c.1210-12 T [5-9], c.1242-35-1242-12GT [8-10], c.744-33GATT [6-8] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction.
Our results showed that the T7 allele is the most common allele in normal and non-ΔF508 CF chromosomes with the frequencies of 93.6% and 100%, respectively. Conversely, T9 was the only allele detected in ΔF508 chromosomes. Moreover, the c.1242-35-1242-12GT analysis showed that (TG)11 repeat was the most common dinucleotide repeat in both, non-ΔF508 and normal chromosomes with the frequencies of 91% and 71%, respectively. The c.744-33GATT and c.869 + 11C > T polymorphism analyses indicated that (GATT)6 and T allele are only found in ΔF508 CF chromosomes. Besides, the [T7-TG11-GATT7-C] haplotype was the most common haplotype in both, normal and non-ΔF508 CF subjects while the [T9-TG10- GATT6-T] haplotype was only detected in CF patients carrying ΔF508 mutation.
Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.
囊性纤维化跨膜电导调节因子（CFTR）基因突变是囊性纤维化（CF）疾病的病因。由于多态性在不同人群中的分布存在差异，因此比较 CFTR 多态性在患者和健康人群中的频率可能有助于进一步确定其在 CF 疾病中的作用。这项研究的结果可以帮助预测产前诊断或新生儿筛查计划中的疾病表型，并确定特定突变与单倍型之间的可能关联。
从 27 个不相关的伊朗西部家庭中采集血液样本，每个家庭至少有一名 CF 患者和 55 个无 CF 病史的对照家庭。在提取 DNA 后，通过自动直接 DNA 测序分析 c.1210-12T[5-9]、c.1242-35-1242-12GT[8-10]、c.744-33GATT[6-8]和 c.869+11C>T 多态性。
我们的结果表明，T7 等位基因是正常和非 ΔF508 CF 染色体中最常见的等位基因，频率分别为 93.6%和 100%。相反，T9 是 ΔF508 染色体中唯一检测到的等位基因。此外，c.1242-35-1242-12GT 分析表明，（TG）11 重复是在非 ΔF508 和正常染色体中最常见的二核苷酸重复，频率分别为 91%和 71%。c.744-33GATT 和 c.869+11C>T 多态性分析表明，（GATT）6 和 T 等位基因仅在 ΔF508 CF 染色体中发现。此外，[T7-TG11-GATT7-C]单倍型是正常和非 ΔF508 CF 受试者中最常见的单倍型，而[T9-TG10-GATT6-T]单倍型仅在携带 ΔF508 突变的 CF 患者中检测到。
我们的研究结果确定了一个信息丰富的单倍型，可用于伊朗的遗传咨询、产前诊断和未来的 CF 筛查。
