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GRADUATE GENOMICS
Problem Set 1

1. Using the numbers provided by the book for the size of the human genome and the number of genes it contains, estimate the density of genes in the genome. Specifically, approximately how many genes would you expect to find in a random stretch of 1 million base pairs (1 Mb)? What issues might you raise with this estimate?

2. Assume that the average human polypeptide has a length of 300 amino acids, and that the average gene requires a control region (regulatory sequences, promoter, etc.) of 500 base pairs. Estimate the minimum size that the human genome could be while containing its current complement of genes. That is, how small could the genome be if all introns, intergenic sequences, repetitive elements, etc. were stripped out?

3. The eukaryotic mitochondrion is theorized to have originated from a free-living bacterium closely related to the extant genus Rickettsia. Similarly, the plant chloroplast is thought to have originated from a free-living cyanobacterium. Using the table below, estimate the gene density (genes/Mb) for mitochondria, rickettsia, chloroplast, and cyanobacterium. What has happened to the genomes of the bacteria as they evolved to become a endosymbiotic organelles?
Genome Size (bp) Number of genes
Human mitochondrion 16,569 37
Rickettsia prowazekii 1,111,523 834
Arabidopsis chloroplast 154,478 128
Synechocystis sp. PCC 6803 (a cyanobacterium) 3,573,470 ~3500

4. If you randomly pick two unrelated humans and compare their genomes, you will find an average of 1 difference per 1200 nucleotides. Any human and any chimpanzee will have an average of 1 difference per 100 nucleotides. Estimate the average total number of nucleotide differences between two humans across the entire genome; and estimate the average total number of differences between any human and any chimpanzee.

5. The Online Mendelian Inheritance in Man database (OMIM) is a resource that shows what genes or genomic regions have been linked to susceptibility to particular diseases.
% - a phenotype for which the molecular basis is unknown.
# - a phenotype for which the molecular basis is known.
* - a gene with one or more alleles that produce a phenotype.
Search for some disease that interests you (look for a # record), and pick a gene that has been linked to this disease. Browse around the OMIM page to learn about this gene. Also, follow the link at right that says ‘Gene Info’ and click on ‘NCBI Gene” to get information from the NCBI database.

What journal article reports a link between this gene and the disease?

What is the normal function of the gene?

What changes to the gene cause the disease phenotype?

Where is the gene located (physical and cytological location)?

What is the exon/intron structure of the gene?

What genes lie near this one on its chromosome?

What is/are the sequence of the protein(s) encoded by the gene?

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1.   According to the book, there are about 23,000 protein coding genes and 3000 genes that code for RNAs. Hence, the total number of genes are 26,000.
The length of the human genome is 3.2 x 109 bp that is 3.2 x 106 Mb.
Hence, approximately about 0.008125 per Mb of the human genome. Thus it appears that a gene should be situated per 1000 Mb of the human genome, which is misleading. Many persons may think that an average human gene is 1000Mb long. However, the density as evident from the above calculation is mostly because a huge span of the human genome contains non-coding regions called “Junk DNA.” Also, the size of the gene is not uniform, and some genes are small while some are large.
2.   According to the information provided the average length of the gene provided = 300 x 3 bp + 500 bp = 1400bp. Hence the minimum size that a human genome could be = 1400bp x number of genes = 14, 00 x 26,000 = 3.64 x 107 bp, that is approximately 100 times less than the actual size...

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