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

Zinc Fingers Proteins Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00340769
• Other study ID #: 999901160
• Secondary ID: 01-E-N160
• Status: Completed
• Phase: N/A
• First received: June 19, 2006
• Last updated: June 30, 2017
• Start date: April 18, 2001
• Est. completion date: December 20, 2006

Study information

• Verified date: December 20, 2006
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: December 20, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

• ELIGIBILITY CRITERIA:

Both genders are eligible.

Ages included children through adulthood.

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

Related Conditions & MeSH terms

• Zinc Fingers Proteins

Locations

Country	Name	City	State
Central African Republic	Ministry of Health and Scientific Research	Bangui
United States	NIEHS, Research Triangle Park	Research Triangle Park	North Carolina
United States	Washington State University	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Environmental Health Sciences (NIEHS)

Countries where clinical trial is conducted

United States,  Central African Republic,