GeneGateway Workbook Answers http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/ggworkbook1.pdf Hereditary Hemochromatosis Worksheet Questions for Activity #1 1) Hemochromatosis is an iron load disorder with characteristics: cirrhosis of the liver, diabetes, hypermelanotic pigmentation of skin, heart failure. A type of cancer, primary hepatocellular carcinoma sometimes occurs and is found in one third of the deaths by this condition. Treatment = bleeding or therapeutic phlebotomy in precirrhotic stages to remove a volume of blood to help lower the amount of iron. 2) gene symbol HLA gene locus 6p21.3 3) Description: A missense mutation in a highly conserved section in the HFE gene causes a cys282-to-tyr (C282Y) substitution. This mutation disrupts the structure and function of the MHC class I protein, which in turn affects its iron absorption from blood. Questions for Activity #2 1) Top half of chromosome 6 on the short arm 2) 1528 total genes 3) 266 genes in region (may depend on region selected) 4) 26 phenotypes in region (may depend on region selected) Questions for Activity #3 1) Function of the gene’s membrane protein product is to regulate proper iron absorption in the body by regulating interaction of the transferrin receptor with transferrin. 2) 9,610 base pairs 3) 7 exons 4) 297 bp of exon 1 5) CDS 1047bp 6) exon 1: 297-221 no codant = 76 7) 2727bp mRNA 8) 2727 mRNA polyA – 1047 CDS = 1680bp Questions for Activity #4 and #5 1) Underline amino acids 23 through 348 or the end of the sequence 2) The two small purple chains are the beta-2-microglobulin, the green and blue chains are HFE 3) The disulfide bond between cysteines 225 and 282 of chain A is lost when the mutation C282Y occurs.