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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,...
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Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
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Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
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DNA structural features and variability of complete MHC locus sequences.

Trudy M Wassenaar1, Terry Harville2, Jonathan Chastain3

  • 1Molecular Microbiology and Genomics Consultants, Zotzenheim, Germany.

Frontiers in Bioinformatics
|July 18, 2024
PubMed
Summary
This summary is machine-generated.

The Human Leukocyte Antigen (HLA) locus, crucial for immunity, shows significant structural DNA variations. New sequencing reveals these variations, aiding disease research and understanding gene expression.

Keywords:
HLA genesMHC loci structural variability -revision 2.2MHC loci structural variability -revision 2.2 DNA structural atlasMHC locuspolymorphismsvisualization

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Area of Science:

  • Genomics
  • Immunogenetics
  • Structural Biology

Background:

  • The Major Histocompatibility Complex (MHC), or Human Leukocyte Antigen (HLA) genes, is a highly variable 5 Mbp region on chromosome 6.
  • This locus encodes critical proteins for immunological response and harbors genetic variations linked to numerous diseases.
  • Local structural DNA features within the MHC locus have been understudied.

Purpose of the Study:

  • To characterize the local structural features of the MHC locus using advanced sequencing technologies.
  • To create structural maps of the complete MHC locus, including diploid haplotypes.
  • To identify variations in DNA structure that may influence gene expression.

Main Methods:

  • Utilized long-read sequencing technology to obtain complete diploid haplotypes of the 5 Mbp MHC locus.
  • Analyzed complete sequences from six different homozygous HLA cell lines.
  • Generated structural maps focusing on DNA stacking energy, position preference, curvature, and repeat variations.

Main Results:

  • Identified significant long-range structural variability across different MHC/HLA sequences.
  • Observed variations in DNA stacking energy, position preference, curvature, and repeat content.
  • Detected local changes in open chromatin structures, potentially impacting gene expression.

Conclusions:

  • Structural maps of the MHC/HLA locus reveal extensive long-range and local DNA variations.
  • These variations, including chromatin structure changes, likely play a role in gene regulation.
  • The generated structural maps are valuable for visualizing HLA-specific structural variations, especially when combined with epigenetic data.