Copy number variation burden on asthma subgenome in normal cohorts identifies susceptibility markers.
OBJECTIVE
Asthma is a complex disease caused by interplay of genes and environment on the genome of an individual. Copy number variations (CNVs) are more common compared to the other variations that disrupt genome organization. The effect of CNVs on asthma subgenome has been less studied compared to studies on the other variations. We report the assessments of CNV burden in asthma genes of normal cohorts carried out in different geographical areas of the world and discuss the relevance of the observation with respect to asthma pathogenesis.


METHODS
CNV analysis was performed using Affymerix high-resolution arrays, and various bioinformatics tools were used to understand the influence of genes on asthma pathogenesis.


RESULTS
This study identified 61 genes associated with asthma and provided various mechanisms and pathways underlying asthma pathogenesis. CCL3L1, ADAM8, and MUC5B were the most prevalent asthma genes. Among them, CCL3L1 was found across all 12 populations in varying copy number states. This study also identified the inheritance of asthma-CNVs from parents to offspring creating the latent period for manifestation of asthma.


CONCLUSIONS
This study revealed CNV burden with varying copy number states and identified susceptibility towards the disease manifestation. It can be hypothesized that primary CNVs may not be the initiating event in the pathogenesis of asthma and additional preceding mutations or CNVs may be required. The initiator or primary CNVs sensitize normal cohorts leading to an increased probability of accumulating mutations or exposure to allergic stimulating agents that can augment the development of asthma.
Genetics and Genomics Lab, Department of Studies in Zoology, University of Mysore, Manasagangotri, Karnataka, India.
Sangeetha
S
Vishweswaraiah
Genetics and Genomics Lab, Department of Studies in Zoology, University of Mysore, Manasagangotri, Karnataka, India.
Avinash M
AM
Veerappa
Department of Pulmonology, JSS Hospital, Karnataka, India.
Padukudru A
PA
Mahesh
Genetics and Genomics Lab, Department of Studies in Zoology, University of Mysore, Manasagangotri, Karnataka, India.
Sareh R
SR
Jahromi
Genetics and Genomics Lab, Department of Studies in Zoology, University of Mysore, Manasagangotri, Karnataka, India. nallurbr@gmail.com.
Nallur B
NB
Ramachandra
Asthma; CCL3L1; DNA copy number variation; genetic markers; inheritance pattern