Article thumbnail

Homozygous Deletion of Six Olfactory Receptor Genes in a Subset of Individuals with Beta-Thalassemia

By Jessica Van Ziffle, Wendy Yang and Farid F. Chehab


Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susceptibility to altered olfaction coupled with the absence of particular olfactory receptor genes will allow phenotype/genotype correlations and vindicate the function of specific olfactory receptors with their cognate ligands. We characterized a 118 kb β-globin deletion and found that its 3′ end breakpoint extends to the neighboring olfactory receptor region downstream of the β-globin gene cluster. This deletion encompasses six contiguous olfactory receptor genes (OR51V1, OR52Z1, OR51A1P, OR52A1, OR52A5, and OR52A4) all of which are expressed in the brain. Topology analysis of the encoded proteins from these olfactory receptor genes revealed that OR52Z1, OR52A1, OR52A5, and OR52A4 are predicted to be functional receptors as they display integral characteristics of G-proteins coupled receptors. Individuals homozygous for the 118 kb β-globin deletion are afflicted with β-thalassemia due to a homozygous deletion of the β-globin gene and have no alleles for the above mentioned olfactory receptors genes. This is the first example of a homozygous deletion of olfactory receptor genes in human. Although altered olfaction remains to be ascertained in these individuals, such a study can be carried out in β-thalassemia patients from Malaysia, Indonesia and the Philippines where this mutation is common. Furthermore, OR52A1 contains a γ-globin enhancer, which was previously shown to confer continuous expression of the fetal γ-globin genes. Thus, the hypothesis that β-thalassemia individuals, who are homozygous for the 118 kb deletion, may also have an exacerbation of their anemia due to the deletion of two copies of the γ-globin enhancer element is worthy of consideration

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1975). A
  2. (2003). A novel deletion causing (epsilon gamma delta beta) degrees thalassaemia in a Chilean family.
  3. (1991). A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.
  4. (2001). A partial deletion of the aspartoacylase gene is the cause of Canavan disease in a family from Mexico.
  5. (1999). A single, large deletion accounts for all the beta-globin gene mutations in twenty families from Sabah (North Borneo), Malaysia. Mutation in brief no.
  6. (2008). Alphathalassaemia in association with beta-thalassaemia patients in Malaysia: a study on the co-inheritance of both disorders.
  7. (1999). An olfactory receptor gene is located in the extended human beta-globin gene cluster and is expressed in erythroid cells.
  8. (2007). Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray.
  9. (1999). Cloning, functional expression and characterization of a human olfactory receptor.
  10. (2000). Comparative structural and functional analysis of the olfactory receptor genes flanking the human and mouse beta-globin gene clusters.
  11. (2001). Evaluation of methods for the prediction of membrane spanning regions.
  12. (2006). Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates.
  13. (2008). Expression analysis of G Protein-Coupled Receptors in mouse macrophages.
  14. (2010). Fetal hemoglobininsickle cellanemia:genome-wide association studies suggest aregulatory region in the 59 olfactory receptor gene cluster.
  15. (1994). Filipino beta-thalassemia due to a large deletion: identification of the deletion endpoints and polymerase chain reaction (PCR)-based diagnosis.
  16. (2007). Genetic elucidation of human hyperosmia to isovaleric acid.
  17. (2010). Genetic modifiers of Hb E/beta0 thalassemia identified by a two-stage genome-wide association study.
  18. (2007). Genetic variation in a human odorant receptor alters odour perception.
  19. (2011). Hamodrakas SJ (2004) TMRPres2D: high quality visual representation of transmembrane protein models.
  20. (2008). High-resolution copy-number variation map reflects human olfactory receptor diversity and evolution.
  21. (2003). Identification of a testicular odorant receptor mediating human sperm chemotaxis.
  22. (1993). Identification of two novel beta zero-thalassemia mutations in a Filipino family: frameshift codon 67 (-TG) and a beta-globin gene deletion.
  23. (1984). Localization of the beta-globin gene by chromosomal in situ hybridization.
  24. (1998). Molecular Basis of beta-Thalassemia in Indonesia: Application to Prenatal Diagnosis.
  25. (1995). Molecular pathology of beta-thalassemia in Indonesia.
  26. (2006). Olfactory dysfunction as a predictor of neurodegenerative disease.
  27. (1998). Prevalence and molecular characterization of beta-thalassemia in Filipinos.
  28. (2002). Processing of gene expression data generated by quantitative real-time RT-PCR.
  29. (2009). Severe intrauterine anemia: a new form of epsilongammagammadeltabeta thalassemia presenting in utero in a Norwegian family.
  30. (1997). Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold.
  31. (1999). Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus Laevis oocytes.
  32. (2007). Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2.
  33. (1989). The breakpoint of a large deletion causing hereditary persistence of fetal hemoglobin occurs within an erythroid DNA domain remote from the beta-globin gene cluster.
  34. (1944). The genetic aspects of primary eunuchoidism.
  35. (2004). The human olfactory receptor gene family.
  36. (1992). Types of thalassemia among patients attending a large university clinic in Kuala Lumpur,