scholarly journals A Data-Driven Approach to Carrier Screening for Common Recessive Diseases

2020 ◽  
Vol 10 (3) ◽  
pp. 140 ◽  
Author(s):  
Anna V. Kiseleva ◽  
Marina V. Klimushina ◽  
Evgeniia A. Sotnikova ◽  
Mikhail G. Divashuk ◽  
Alexandra I. Ershova ◽  
...  
Keyword(s):  
Population Based ◽  
Carrier Screening ◽  
Russian Population ◽  
Genotyping Platform ◽  
Number Of Genes ◽  
Antitrypsin Deficiency ◽  
Data Driven Approach ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Custom Panel

Genetic screening is an advanced tool for reducing recessive disease burden. Nowadays, it is still unclear as to the number of genes or their variants that are necessary for effective screening. This paper describes the development of a carrier screening custom panel for cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss consisting of 116 variants in the CFTR, PAH, SERPINA1, and GJB2 genes. The approach is based on the cheapest and fastest method, on using a small number of genes, and on the estimation of the effectiveness of carriers’ detection. The custom panel was tested on a population-based cohort that included 1244 participants. Genotypes were determined by the TaqMan OpenArray Genotyping platform on the QuantStudio 12K Flex Real-Time PCR System. The frequency of heterozygotes in the Russian population was 16.87% or 1:6 (CI95%: 14.76–19.00% by Clopper-Pearson exact method): in CFTR—2.81% (1:36), PAH—2.33% (1:43), SERPINA1—4.90% (1:20), and GJB2—6.83% (1:15). The data on allele frequencies were obtained for the first time on a Russian population. The panel allows us to identify the vast majority of carriers of recessive diseases in the population. It is an effective approach to carrier screening for common recessive diseases.

scholarly journals COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

2017 ◽  
Vol 26 (146) ◽  
pp. 170068 ◽  
Author(s):  
Haitham S. Al Ashry ◽  
Charlie Strange
Keyword(s):  
General Population ◽  
Population Based ◽  
Rapid Decline ◽  
Augmentation Therapy ◽  
Ongoing Debate ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Study Designs

Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2–5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case–control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.

scholarly journals Diagnosis of alpha-1 antitrypsin deficiency: a population-based study

2016 ◽  
pp. 999 ◽  
Author(s):  
Marc Miravitlles ◽  
Miriam Barrecheguren ◽  
Mónica Monteagudo ◽  
Pere Simonet ◽  
Carl Llor ◽  
...  
Keyword(s):  
Population Based ◽  
Population Based Study ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Dawn McGee ◽  
Laura Schwarz ◽  
Rebecca McClure ◽  
Lauren Peterka ◽  
Farshid Rouhani ◽  
...  
Keyword(s):  
Liver Disease ◽  
Population Based ◽  
Medication History ◽  
Antitrypsin Deficiency ◽  
Clinical Diagnoses ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Study Population ◽  
Alpha 1 Antitrypsin ◽  
Study Participants ◽  
Similar Incidence

Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease.Objective. The current study examined the clinical features of the PiSS genotype.Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators.Results. 12/19 (63.2%) study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4%) control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%).Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests.

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