Department of Biotechnology, Assam University, Silchar 788011, Assam, India.
Department of Biotechnology, Assam University, Silchar 788011, Assam, India.
Gene. 2020 Jul 15;747:144673. doi: 10.1016/j.gene.2020.144673. Epub 2020 Apr 15.
Krabbe disease is one of the rarest autosomal recessive disorders in human, caused by mutation in the GALC (β-galactosylceramidase) gene, resulting in several mental and physical health issues. Due to its rarity and phenotypic heterogeneity, diagnosis rate of this disease is very low. This study generated information on the recessive allele frequency dynamics of GALC gene across 15 global populations, with the highest frequency detected in Druze (Israel) population and the lowest frequency in Turkey and the United States. The recessive allele would take more time period (about 24,975 years) to be completely removed from the population having the lowest frequency and vice versa. The codon usage patterns of four isoforms of GALC gene revealed that a few synonymous codons were used more frequently than others in the isoforms. The codon AGA (arginine) was found to be overrepresented in GALC gene, except for galactocerebrosidase isoform a precursor. Further, GALC gene showed low codon usage bias (CUB) as evident from high ENC values (55.7-58.2), with A/T ending codons more preferred to G/C ending codons. CUB analysis elucidated the dual role of mutational pressure (major role) and natural selection (minor role) in GALC gene evolution.
克拉伯病是人类最罕见的常染色体隐性遗传病之一，由半乳糖脑苷脂酶（GALC）基因突变引起，可导致多种精神和身体健康问题。由于其罕见性和表型异质性，这种疾病的诊断率非常低。本研究在 15 个全球人群中生成了关于 GALC 基因隐性等位基因频率动态的信息，在以色列德鲁兹人群中检测到的频率最高，在土耳其和美国检测到的频率最低。在频率最低的人群中，隐性等位基因需要更长的时间（约 24975 年）才能被完全清除，反之亦然。GALC 基因的四个同工型的密码子使用模式表明，在同工型中，一些同义密码子比其他密码子使用得更频繁。除了半乳糖脑苷脂酶 a 前体同工型外，GALC 基因中的精氨酸密码子 AGA 被发现过度表达。此外，GALC 基因的密码子使用偏性低（CUB），表现为高ENC 值（55.7-58.2），A/T 结尾密码子比 G/C 结尾密码子更受欢迎。CUB 分析阐明了突变压力（主要作用）和自然选择（次要作用）在 GALC 基因进化中的双重作用。
