Mentor Areas
The primary focus of this laboratory is to understand the molecular basis of human genetics diseases and provide testing for the individuals affected with these diseases. Students who work in our laboratory gain valuable, practical experience in translational basic science research that complements clinical diagnostic testing.
Description:
In humans, including most female mammals, one X chromosome is randomly inactivated to compensate for the fact that females have twice as many X-chromosome genes as males do. This phenomenon is called dosage compensation. Although the choice of which of the two X's is inactivated is entirely random, not all women have a 50:50 ratio of cells with one or the other X chromosomes active. A number of different mechanisms lead to extremely skewed ratios and this can result in expression of the phenotype of X-linked recessive disorders in females as well as asymptomatic females in X-linked dominant conditions. (Semin Reprod Med. 2001 Jun;19(2):183-91).
The randomness of the inactivation processes is evaluated by looking into the ARA-locus on X-chromosome. For measurement of skewing of the X-chromosome inactivation, the HUMARA assay is used. This involves PCR amplification of the polymorphic CAG repeat at the HUMARA locus(2,17) locus and is performed in tandem on undigested (6-FAM–labeled primer) and on HpaII-digested (fluoresecntly-labeled primer) DNA. Amplification products are analyzed on an ABI 3500 genetic analyzer (Applied Biosystems, Foster City, CA) to determine the area under the curve (AUC) for each allele. Usually the 2 alleles are of different length and identifies the respective alleles derived from the parents. Skewed X inactivation occurring by chance appears to be rare, but has been reported in a series of phenotypically normal females. Skewing to the extent of >80:20 was observed in 8% of cases and to >95:5 in 0.8% of cases. Sensitivity can vary due to the potential for markers to be uninformative; uninformative markers occur in ~1% of cases.
This project will involve student working on assaying for 3 additional markers on X-chromosome to find out: a) whether the cases deemed uninformative by the ARA assay can be evaluated based on the additional loci; b) to see whether disease expression better correlates with any of the additional loci compared to the ARA locus.
Evaluating for skewed patterns of X-inactivation can be useful in analysis and diagnosis of X-linked conditions in females affected with X-linked diseases.
Preferred Qualifications
Experience in molecular biology or genetics is not necessary, but helpful.
Experience in Microsoft Excel a bonus.
Details:
Preferred Student Year
Junior, Senior
Academic Term
Fall, Spring, Summer
I prefer to have students start during the above term(s).Volunteer
Yes
Yes indicates that faculty are open to volunteers.Paid
No
Yes indicates that faculty are open to paying students they engage in their research, regardless of their work-study eligibility.Work Study
No
Yes indicates that faculty are open to hiring work-study-eligible students.