A 12-year-old boy is evaluated in the clinic due to excessive bleeding following a tooth extraction. The patient also develops large bruises after only minor injury but has had no major bleeding episodes in the past. His maternal uncle died from an intracranial hemorrhage. Laboratory testing reveals decreased coagulation factor VIII activity levels. A referral is made to a clinical geneticist, who suspects that the patient has a deletion mutation in the enhancer sequence of the factor VIII gene. This mutation has resulted in decreased transcription of factor VIII by RNA polymerase II. Which of the following is the most accurate statement regarding the abnormal genetic sequence in this patient?

Question

A 12-year-old boy is evaluated in the clinic due to excessive bleeding following a tooth extraction.  The patient also develops large bruises after only minor injury but has had no major bleeding episodes in the past.  His maternal uncle died from an intracranial hemorrhage.  Laboratory testing reveals decreased coagulation factor VIII activity levels.  A referral is made to a clinical geneticist, who suspects that the patient has a deletion mutation in the enhancer sequence of the factor VIII gene.  This mutation has resulted in decreased transcription of factor VIII by RNA polymerase II.  Which of the following is the most accurate statement regarding the abnormal genetic sequence in this patient?

Quizplus · Accepted Answer

11ec160b_3777_2825_9249_05eacb27a094_MD0001_00 This patient has hemophilia A, an X-linked recessive disorder characterized by easy bruising and excessive bleeding due to a deficiency in coagulation factor VIII. The disorder can be caused by a variety of different mutations in the factor VIII gene, including deletions in the enhancer sequence. In eukaryotic gene transcription, nuclear RNA polymerase II uses a DNA template to generate complementary mRNA, which is then processed and translated into protein. Eukaryotic genes have associated promoter and enhancer sequences that mediate transcription. Promoter sequences directly bind general transcription factors and RNA polymerase II upstream from the gene locus, which is necessary for the initiation of transcription (Choices C and E). There are 2 types of eukaryotic promoter regions: the TATA, or Hogness, box, which is located approximately 25 bases upstream from the gene being transcribed; and the CAAT box, which is 70-80 bases upstream from the gene. In contrast to promoters, enhancer sequences bind activator proteins that facilitate bending of DNA. DNA bending allows activator proteins to interact with general transcription factors and RNA polymerase II at the promoter, increasing the rate of transcription (Choice D). Enhancers can be located upstream or downstream from the gene being transcribed and may be near the gene or thousands of base pairs away (Choice B). They have also been identified both within introns of the gene being transcribed as well as on separate chromosomes. Silencers are similar to enhancers, but they decrease transcription rates by binding repressor proteins. Educational objective: Enhancers and silencers may be located upstream, downstream, or within a transcribed gene; these gene sequences function to increase and decrease the rate of transcription, respectively. In contrast, promoter regions are typically located 25 or 75 bases upstream from their associated genes and function to initiate transcription. __________ References: Regulatory regions in DNA: promoters, enhancers, silencers, and insulators. (http://www.ncbi.nlm.nih.gov/pubmed/20827584)

A 12-Year-Old Boy Is Evaluated in the Clinic Due to Excessive