Prevalence of a Non-Expressing 11B Mutation in Aka Peoples of the Central African Republic

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00340769
First received: June 19, 2006
Last updated: March 5, 2008
Last verified: December 2006
  Purpose

The CCCH tandem zinc finger proteins are members of a small family of proteins that regulate the stability of certain types of mRNA containing so-called class II AU-rich elements in their 3'-untranslated regions. The best studied member of this protein family, tristetraprolin (TTP), exerts this destabilizing effect on at least two mRNAs coding for physiologically and medically important cytokines, tumor necrosis factor alpha and granulocyte macrophage colony stimulating factor. The physiological functions of the other two members of this protein family in mammals, 11B and 11D, are not known, but in experimental transfection studies they too can destabilize mRNAs containing this type of AU-rich element.

As part of the Environmental Genome Project, we resequenced the protein coding portions of the human genes encoding these three proteins, and uncovered a dinucleotide splice site mutation in the 11B gene in one of 144 alleles sequenced. We showed that this mutation created a novel restriction fragment length polymorphism, and that this mutation resulted in the failure of splicing and expression of the mRNA encoded by the mutant allele. Based on our previous data with mice completely deficient in TTP, we anticipate that complete deficiency of this protein, and possibly its partial deficiency, would result in human disease.

The mutant allele was from an anonymous adult Aka Pygmy women from the Central African Republic. We propose to genotype up to 1000 members of this ethnic group after obtaining buccal cell DNA from them. This will give us an approximate idea of the prevalence of this mutation in this population. If the mutation is found in a significant number of living individuals in this initial screen, then we will propose a later study of the individuals who have this genotype and their families. This second study, which will be reviewed separately, will attempt to correlate this genotype with a human trait or phenotype and possible y treatable human disease.


Condition
Zinc Fingers Proteins

Study Type: Observational
Official Title: Prevalence of a Non-Expressing 11B Mutation in Aka Peoples of the Central African Republic

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 0
Study Start Date: April 2001
Estimated Study Completion Date: December 2006
Detailed Description:

The CCCH tandem zinc finger proteins are members of a small family of proteins that regulate the stability of certain types of mRNA containing so-called class II AU-rich elements in their 3'-untranslated regions. The best studied member of this protein family, tristetraprolin (TTP), exerts this destabilizing effect on at least two mRNAs coding for physiologically and medically important cytokines, tumor necrosis factor alpha and granulocyte macrophage colony stimulating factor. The physiological functions of the other two members of this protein family in mammals, 11B and 11D, are not known, but in experimental transfection studies they too can destabilize mRNAs containing this type of AU-rich element.

As part of the Environmental Genome Project, we resequenced the protein coding portions of the human genes encoding these three proteins, and uncovered a dinucleotide splice site mutation in the 11B gene in one of 144 alleles sequenced. We showed that this mutation created a novel restriction fragment length polymorphism, and that this mutation resulted in the failure of splicing and expression of the mRNA encoded by the mutant allele. Based on our previous data with mice completely deficient in TTP, we anticipate that complete deficiency of this protein, and possibly its partial deficiency, would result in human disease.

The mutant allele was from an anonymous adult Aka Pygmy women from the Central African Republic. We propose to genotype up to 1000 members of this ethnic group after obtaining buccal cell DNA from them. This will give us an approximate idea of the prevalence of this mutation in this population. If the mutation is found in a significant number of living individuals in this initial screen, then we will propose a later study of the individuals who have this genotype and their families. This second study, which will be reviewed separately, will attempt to correlate this genotype with a human trait or phenotype and possible treatable human disease.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • ELIGIBILITY CRITERIA:

Both genders are eligible.

Ages included children through adulthood.

Must be willing and able to participate and understand the explanations and instructions.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00340769

Locations
United States, North Carolina
NIEHS, Research Triangle Park
Research Triangle Park, North Carolina, United States, 27709
United States, Washington
Washington State University
Vancouver, Washington, United States, 98686
Central African Republic
Ministry of Health and Scientific Research
Bangui, Central African Republic
Sponsors and Collaborators
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00340769     History of Changes
Other Study ID Numbers: 999901160, 01-E-N160
Study First Received: June 19, 2006
Last Updated: March 5, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cytokines
Inflammation
mRNA Stability
Pygmy
Zinc Finger Proteins
Ethnic Group

ClinicalTrials.gov processed this record on April 15, 2014