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Duchenne muscular dystrophy (DMD) is an X-linked disease

  • Duchenne muscular dystrophy (DMD) is an X-linked disease for which prenatal diagnostic testing can be performed. Has prenatal genetic testing increased the detection rate of this disease, compared to prior diagnostic methods? If so, how? If not, why? In case the fetus is diagnosed with DMD and parents decide to terminate the pregnancy, are there chances that the next child will also be a carrier of the disease?
  • Jane Hill’s husband, Charlie Marlow, has hemophilia A when he marries Hill, who does not have the disorder. Jane’s parents also do not have hemophilia, but her brother Steve Hill does. What is the probability that the Marlows’ son will have the disorder? What is the probability that their daughter will have hemophilia? Are there chances that their daughter will be a carrier of this disorder?
  • Which DNA sequence will encode for at least five amino acids? Change three different bases separately (either by addition or deletion) and write the corresponding amino acid sequences that result from these modifications.
  • Using the Internet, search and describe a genetic disorder (other than ?-thalassemia mental retardation syndrome, immunodeficiency–centromeric instability–facial anomalies [ICF] syndrome, Rett syndrome, and Rubinstein-Taybi syndrome) that results from aberrant chromatin remodeling. Does the disorder result from adding or deleting acetyl, methyl, or phosphate groups? Explain. Does the abnormal chromatin remodeling affect other genes?
  • Using the Internet, search and describe a genetic disorder that results from aberrant gene splicing. How does alternative splicing affect the disorder? Where in the gene does the aberrant splicing occur?
  • Identified a gene, other than BRCA1 (breast cancer 1, early onset), that increases the risk of developing breast cancer when mutant. In addition, described the process or mechanism that the mutation of your chosen gene disrupts.
 
  • Explained how alternate splicing can complicate the study of mutations in the BRCA1. Also, compared and described hereditary germline cancers such as those caused by BRCA1 mutations and cancers that result from two somatic mutations in the same gene in the same cell.

Chromosomal Mutations

Gene mutations can occur spontaneously or could be induced by exposure to chemicals or radiations. Mutations are of various types, ranging from point mutations to expanding repeats. Each mutation is classified by the way it alters the DNA.

Types of Mutation
A sentence made of three-letter words can provide an analogy to the effect of mutations on a gene’s DNA sequence.
Normal THE ONE BIG FLY HAD ONE RED EYE
Missense THQ ONE BIG FLY HAD ONE RED EYE
Nonsense THE ONE BIG
Frameshift THE ONE QBI GFL YHA DON ERE DEY
Deletion THE ONE BIG HAD ONE RED EYE
Insertion THE ONE BIG WET FLY HAD ONE RED EYE
Duplication THE ONE BIG FLY FLY HAD ONE RED EYE
Expanding mutation  
Generation 1 THE ONE BIG FLY HAD ONE RED EYE
Generation 2 THE ONE BIG FLY FLYFLY HAD ONE RED EYE
Generation 3 THE ONE BIG FLY FLYFLYFLYFLY HAD ONE RED EYE
  • Complete the following discussions:

    • Describe a genetic disorder resulting from one of the mutations listed in the table. What is the mode of inheritance of your chosen disorder? What does the affected gene sequence look like in comparison to the normal sequence? What is the change in the amino acid sequence as a result of the disorder?
    • Describe the DNA repair process in eukaryotes. Why do you think this process is absent in mitochondrial DNA? What properties of mitochondrial DNA prevent it from repairing itself?
    • Describe two purposes of performing a karyotype (other than detecting abnormal chromosome numbers). In your opinion, should karyotyping be performed in the early stages of pregnancy to look for genetic disorders? Why or why not?
    • Identify two types of chromosomal abnormalities that can result from addition, deletion, or duplication of genetic material and describe how it happens. Describe a genetic disorder that can result from one of the aberrations identified by you.

 

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