Genetic Restriction of HIV1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 struc

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Genetic Restriction of HIV-1 Infection and
Progression to AIDS by a Deletion Allele of the
CKR5 structural gene

• Alexis Morante
• March 2, 2005
• Bio-475
• Dr. Peter Lin

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CKR5 and Delta 32

• CKR5 is a chemokine
• Relationship between CKR5 and receptors
• Deletion of delta 32 base pair leading to frame
  shift in amino acid
• Addition/deletion no divisible by three causes a
  frame shift (33 would have no frame shift).

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Rationale

• Variation of allele and genotypic frequency
  between HIV positive and HIV negative
• Based on the polymorphisms, potential involvement
  in retroviral infection, and their genetic
  location

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Recessive and Dominant phenotype

• Recessive phenotype restriction is expressed with
  two copies.
• Dominant phenotype is expressed with one allele.
• Independent variable HIV-1 positive vs HIV-1
  negative.
• Dependant variable Genotypic distribution
  between HIV infected and HIV uninfected groups

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Genetic Markers and HIV infection
Dean, M. et al. 1996. Genetic restrictions of
HIV-1 infection and progression to AIDS by a
deletion allele of the CKR5 structural gene.
Science 273 1858-1862.
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CKR5 genotype distribution among HIV-1 positive
and HIV-1 negative in the same risk group

• 2 copies of the mutant CKR5 allele
• Infected vs uninfected genotype distribution
• This chart is the best explanation for table 2 in
  Dean et al. article

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Conclusion

• CKR5 was the most resistant of all of the alleles
• CKR5 with two pairs of mutated alleles are found
  only in HIV- negative individuals
• In CKR5 homozygous pair allows the individual to
  remain HIV negative
• Prevents binding and infection

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Reference

• Dean, M. et.al. 1996. Genetic Restriction of
  HIV-1 Infection and Progression to AIDS by a
  Deletion Allele of the CKR5 Structural Gene.
  Science 2731858-1862
• OBrien, S. and M. Dean. 1997. The Search of
  AIDS-Resistance Gene.  Scientific American 44-51