Cystic fibrosis (CF) is a severe autosomal recessive disorder in humans that results from a chloride ion channel defect in epithelial cells. More than 500 mutations have been identified in the 24 exons of the responsible gene (CFTR, or cystic fibrosis transmembrane regulator), including dozens of different missense mutations, frameshift mutations, and splice-site defects. Although all affected CF individuals demonstrate chronic obstructive lung disease, there is variation in whether or not they exhibit pancreatic enzyme insufficiency (PI). Speculate as to which types of mutations are likely to give rise to less severe symptoms of CF, including only minor PI. Some of the 300 sequence alterations that have been detected within the exon regions of the CFTR gene do not give rise to cystic fibrosis. Taking into account your knowledge of the genetic code, gene expression, protein function, and mutation, describe why this might be so.
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- Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene that encodes dystrophin, a large protein that plays an important role in the development of normal muscle fibers. The Dystrophin gene is immense, spanning 2.5 million base pairs, and includes 79 exons and 78 introns. Many of the mutations that cause DMD produce premature stop codons, which bring protein synthesis to a halt, resulting in a greatly shortened and nonfunctional form of dystrophin. Some geneticists have proposed treating DMD patients by introducing small RNA molecules that cause the spliceosome to skip the exon containing the stop codon (A. Goyenvalle et al., 2004. Science 306:1796–1799). The introduction of the small RNAs will produce a protein that is somewhat shortened because an exon is skipped and some amino acids are missing, but it may still result in a protein that has some function. The small RNAs, antisense RNAs, used for exon skipping are complementary to…arrow_forwardDuchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene that encodes dystrophin, a large protein that plays an important role in the development of normal muscle fibers. The dystrophin gene is immense, spanning 2.5 million base pairs, and includes 79 exons and 78 introns. Many of the mutations that cause DMD produce premature stop codons, which bring protein synthesis to a halt, resulting in a greatly shortened and nonfunctionalform of dystrophin. Some geneticists have proposed treating DMD patients by causing the spliceosome to skip the exon containing the stop codon. Exon skipping would produce a protein that is somewhat shortened (because an exon is skipped and some amino acids are missing), but might still result in a protein that had some function (A. Goyenvalle et al. 2004. Science 306:1796–1799). Propose a possible mechanism to bring about exon skipping for the treatment of DMD.arrow_forwardHuntington disease (HD) is an inherited neurodegenerative disorder characterized by gradual, irreversible impairment of psychological, motor, and cognitive functions. Symptoms typically appear in middle age, but onset can occur at almost any age, and the course of the disease can range from 15 to 20 years. The molecular basis of HD is becoming better understood, and the genetic mutation has been traced to a gene that encodes a large protein of unknown function. In individuals who will not develop HD, a region of the gene that encodes the N-terminus of this protein has a sequence of CAG codons (for glutamine) repeated 6 to 39 times in succession. In individuals with adult-onset HD, this codon (3 nucleotides) is typically repeated 40 to 55 times In those with childhood-onset HD, it is repeated more than 70 times. *codon: refers to the 3 nucleotides that code for amino acid. A small portion of the coding sequence of the HD gene is given below. The nucleotide sequence of the DNA is…arrow_forward
- Diamond–Blackfan anemia (DBA) is a rare, dominant genetic disorder characterized by bone marrow malfunction, birth defects, and a predisposition to certain cancers. Infants with DBA usually develop anemia in the first year of life, have lower than normal production of red blood cells in their bone marrow, and have a high risk of developing leukemia and bone cancer. At the molecular level, DBA is caused by mutations in any one of 10 genes that encode ribosomal proteins. The first-line therapy for DBA is steroid treatment, but more than half of affected children develop resistance to the drugs and in these cases, treatment is halted. DBA can be treated successfully with bone marrow or stem cell transplants from donors with closely matching immune system markers. Trans- plants from unrelated donors have significant levels of complications and mortality. 1. Given that a faulty ribosomal protein is the culprit and causes DBA, discuss the possible role of normal ribosomal proteins. Why might…arrow_forwardDiamond–Blackfan anemia (DBA) is a rare, dominant genetic disorder characterized by bone marrow malfunction, birth defects, and a predisposition to certain cancers. Infants with DBA usually develop anemia in the first year of life, have lower than normal production of red blood cells in their bone marrow, and have a high risk of developing leukemia and bone cancer. At the molecular level, DBA is caused by mutations in any one of 10 genes that encode ribosomal proteins. The first-line therapy for DBA is steroid treatment, but more than half of affected children develop resistance to the drugs and in these cases, treatment is halted. DBA can be treated successfully with bone marrow or stem cell transplants from donors with closely matching immune system markers. Trans- plants from unrelated donors have significant levels of complications and mortality. QUESTIONS: 1. Given that a faulty ribosomal protein is the culprit and causes DBA, discuss the possible role of normal ribosomal…arrow_forwardThe D1S80 locus is located on human chromosome 1 and is characterized by a repeating 16 base pair (bp) sequence. Alleles for this locus vary depending on the number of repeats present, thus affecting the size of the locus. The D1S80 locus also contains two conserved sequences, a 32bp sequence at one end and a 113bp sequence at the other end. If the DNA of an individual is targeted for D1S80 amplification, and one of the resulting amplicons is approximately 785bp in size, how many repeats would be present in this D1S80 allele? The amplicon of interest is indicated by a red arrow in the diagram below.arrow_forward
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- The SARS-CoV-2 genome has a cap at its 5'-end that is the same as the one seen on most human mRNA molecules. The nsp12 RNA-dependent RNA polymerase acts like cellular RNA polymerase and initiates RNA synthesis by synthesizing a dinucleotide from two nucleoside triphosphates. What other enzymes are needed to add a cap to the nsp12 product? Describe the chemical nature of the products of each of these enzymesarrow_forwardThe mRNA sequence 5' AUG AAA CAG GGA UAA 3' encodes a particular peptide of interest to your research team. You have identified a new alternate allele of the sequence 5' AUG AAG CAG GGA UAA 3'. What type of mutation does this alternate sequence illustrate?arrow_forwardThe genomes of most multicellular eukaryotes encode~25,000 genes, yet their proteomes contain over 200,000proteins. Propose two processes that, taken together, account for this discrepancyarrow_forward
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