Identifying allele frequencies may aid in selecting the diagnostic method for alpha-1 antitrypsin deficiency (AATD), cystic fibrosis (CF), and other autosomal recessive diseases, as stated in a study recently published in the Journal of Personalized Medicine.

“This study provides new [allele frequency] data for variants associated with CF, [phenylketonuria], A1ATD, and [sensorineural hearing loss] as well as a review of genotyping methods that are usually used for carrier screening,” the authors wrote.

The study included 3821 participants from Russia that had no relationship between them. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) detected 38 variants in the CFTR and SERPINA1 genes involved in the pathogenesis of CF and AATD, respectively, along with other 2 genes implicated in different genetic pathologies such as phenylketonuria and sensorineural hearing loss. To achieve this, the researchers created a custom panel with 115 known mutations in all 4 genes.

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“The comparison of genotyping platforms revealed the following advantages of real-time PCR: relatively low cost, simple genotyping data analysis, and easier detection of large indels, while NGS showed better accuracy of variants identification and capability for detection of additional pathogenic variants in adjacent regions,” the authors explained.

Interestingly, when comparing these findings to data from non-Finnish European populations, 23 allele frequency showcased statistically significant differences, including 7 CFTR variants: rs397508612, CFTRdele2,3, rs113993960, rs121908793, rs397508686, rs75039782, rs78655421; and 3 SERPINA1 variants: rs17580, rs28929474, rs28931570, as reported by Sotnikova et al.

The researchers concluded that the best genotyping method for each disorder should be chosen according to the number of variants analyzed in this study while considering economic circumstances. For example, the authors recommend using the TaqMan method for diseases with fewer variants. Conversely, the NGS method could be superior for entities with a higher number of variants since it demonstrated a better detection capacity.


Sotnikova E, Kiseleva A, Kutsenko V, et al. Identification of pathogenic variant burden and selection of optimal diagnostic method is a way to improve carrier screening for autosomal recessive diseases. J Pers Med. Published July 12, 2022. doi:10.3390/jpm12071132