Related Experiment Video

Updated: Aug 25, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Disease-associated variants in PYPAF1 and NOD2 result in similar alterations of conserved sequence

Mario Albrecht1, Thomas Lengauer, Stefan Schreiber

  • 1Max-Planck-Institute for Informatics, Stuhlsatzenhausweg 85, 66123 Saarbrücken, Germany. maario.albrecht@mpi-sb.mpg.de

Bioinformatics (Oxford, England)
|November 25, 2003
PubMed

Insights

Sequence variations in PYPAF1/CIAS1 and NOD2/CARD15 genes link to autoinflammatory diseases. These variants may impair NTP-hydrolysis in conserved protein regions, suggesting evolutionary gene duplication contributes to disease families.

Area of Science:

  • Genetics and Molecular Biology
  • Immunology
  • Evolutionary Biology

Background:

  • Sequence variations in PYPAF1/CIAS1 and NOD2/CARD15 are linked to autoinflammatory diseases.
  • These diseases, despite clinical differences, share underlying inflammatory pathways.

Purpose of the Study:

  • To investigate the impact of sequence variations in PYPAF1/CIAS1 and NOD2/CARD15.
  • To explore the functional consequences of these variations on protein domains and evolutionary relationships.

Main Methods:

  • Multiple sequence alignment of homologous proteins.
  • Analysis of missense variants within conserved regions of the NTPase domain.

Main Results:

  • Several missense variants were identified in highly conserved regions of the NTPase domain.
  • These variations potentially impair NTP-hydrolysis.
  • A specific variation was found identically in both PYPAF1 and NOD2 at the same alignment position.

Conclusions:

  • Evolutionary gene duplication can lead to disease families.
  • Variants affecting conserved sequences similarly can contribute to shared pathophysiology across related diseases.

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Related Concept Videos

Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...