Background

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.

Methods

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], [6], [7], [8], [9]], c.1242-35-1242-12GT [[8], [9], [10]], c.744-33GATT [[6], [7], [8]] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction.

Results

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.

Conclusions

Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.

中文翻译：

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正常和突变CFTR基因上CFTR基因的单倍型分析。

背景

囊性纤维化跨膜电导调节剂（CFTR）基因的突变负责囊性纤维化（CF）疾病。由于多态性在人群中的分布不同，因此患者和健康人群中CFTR多态性频率的比较可以进一步确定其在CF疾病中的作用。从这项研究中获得的结果可能有助于在产前诊断或新生儿筛查程序中预测疾病表型，以及确定单倍型与特定突变之间的可能关联。

方法

从27个无关的西伊朗家庭中采集的血液样本至少包含一名CF患者和55名无CF病史的对照家庭。分析了样品的c.1210-12 T [[5]，[6]，[7]，[8]，[9]，c.1242-35-1242-12GT [[8]，[9]， [10]，c.744-33GATT [[6]，[7]，[8]]和c.869 + 11C> T多态性，通过DNA提取后的自动直接DNA测序实现。

结果

我们的结果表明，T7等位基因是正常和非ΔF508CF染色体中最常见的等位基因，频率分别为93.6％和100％。相反，T9是在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ΔF508CF染色体中发现。此外，在正常和非ΔF508CF受试者中，[T7-TG11-GATT7-C]单倍型是最常见的单倍型，而仅在带有ΔF508突变的CF患者中检测到[T9-TG10-GATT6-T]单倍型。

结论

我们的发现确定了可用于伊朗的CF的遗传咨询，产前诊断和未来筛查的信息丰富的单倍型。