2nd Semester BOW #1 (4 Gene Sequences)

Gene 1:
Huntingtin is a disease gene linked to Huntington's
disease, a neurodegenerative disorder characterized by loss of

            striatal neurons. This is thought to be caused by an expanded,
            unstable trinucleotide repeat in the huntingtin gene, which
            translates as a polyglutamine repeat in the protein product. A
            fairly broad range in the number of trinucleotide repeats has been
            identified in normal controls, and repeat numbers in excess of 40
            have been described as pathological. The huntingtin locus is large,
            spanning 180 kb and consisting of 67 exons. The huntingtin gene is
            widely expressed and is required for normal development. It is
            expressed as 2 alternatively polyadenylated forms displaying
            different relative abundance in various fetal and adult tissues.
            The larger transcript is approximately 13.7 kb and is expressed
            predominantly in adult and fetal brain whereas the smaller
            transcript of approximately 10.3 kb is more widely expressed. The
            genetic defect leading to Huntington's disease may not necessarily
            eliminate transcription, but may confer a new property on the mRNA
            or alter the function of the protein. One candidate is the
            huntingtin-associated protein-1, highly expressed in brain, which
            has increased affinity for huntingtin protein with expanded
            polyglutamine repeats. This gene contains an upstream open reading
            frame in the 5' UTR that inhibits expression of the huntingtin gene
            product through translational repression. [provided by RefSeq, Jul
            2008].

Gene 2:  

This gene encodes a protein that is one of the two

components of elastic fibers. The encoded protein is rich in
            hydrophobic amino acids such as glycine and proline, which form
            mobile hydrophobic regions bounded by crosslinks between lysine
            residues. Deletions and mutations in this gene are associated with
            supravalvular aortic stenosis (SVAS) and autosomal dominant cutis
            laxa. Multiple transcript variants encoding different isoforms have
            been found for this gene. [provided by RefSeq, Jul 2008].

Gene 3:  

Alzheimer's disease (AD) patients with an inherited form

of the disease carry mutations in the presenilin proteins (PSEN1 or
            PSEN2) or the amyloid precursor protein (APP). These disease-linked
            mutations result in increased production of the longer form of
            amyloid-beta (main component of amyloid deposits found in AD
            brains). Presenilins are postulated to regulate APP processing
            through their effects on gamma-secretase, an enzyme that cleaves
            APP. Also, it is thought that the presenilins are involved in the
            cleavage of the Notch receptor such that, they either directly
            regulate gamma-secretase activity, or themselves act are protease
            enzymes. Two alternatively spliced transcript variants encoding
            different isoforms of PSEN2 have been identified. [provided by
            RefSeq, Jul 2008].

Gene 5:     

This gene encodes a member of the fibrillin family. The
            encoded protein is a large, extracellular matrix glycoprotein that
            serve as a structural component of 10-12 nm calcium-binding
            microfibrils. These microfibrils provide force bearing structural
            support in elastic and nonelastic connective tissue throughout the
            body. Mutations in this gene are associated with Marfan syndrome,
            isolated ectopia lentis, autosomal dominant Weill-Marchesani
            syndrome, MASS syndrome, and Shprintzen-Goldberg craniosynostosis
            syndrome. [provided by RefSeq, Jul 2008].