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Immunogenetic:Immunoglobulin gene
Rearrangement
Farshid Yeganeh PhD
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Virtually any substance can be the target of an antibody response.
"Beadle and Tatum in 1941
One gene-one polypeptide hypothesis“
Dreyer and Bennett postulated in 1965 that each antibody chain is actually encoded by at least two genes, one variable and the other constant
Susumu Tonegawa (1987). Nobel Prize in Physiology or Medicine
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Lymphocyte Development and Antigen Receptor Gene Rearrangement
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Germline organization of human Ig loci.
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Germline organization of human TCR loci.
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Domains of Ig and BCR/TCR proteins
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12/23 rule Recombination occurs between two segments only if one of the
segments is flanked by a 12-nucleotide spacer and the other is
flanked by a 23-nucleotide spacer
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V(D)J recombinatio
n.
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Checkpoint in lymphocyte maturation
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Junctional diversity
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Sequential events during
V(D)J recombination
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Diversity of antigen receptor genes.
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Ig heavy and light chain
gene recombination
and expression.
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Coexpression of IgM and IgD.
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Ataxia telangiectasia, which is caused by mutations in the DNA -PKcs -family kinase ATM, a known DNA repair protein.
In humans, mutations in RAGl or RAG2 that result in partial V(D)J recombinase activity are responsible for an inherited disorder called Omenn syndrome.
Clinical view
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David Vetter September 21, 1971 – February 22, 1984
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