Worksheet - COMPARATIVE MAPPING 1

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1 Worksheet - COMPARATIVE MAPPING 1 The arrangement of genes and other DNA markers is compared between species in Comparative genome mapping. As early as 1915, the geneticist J.B.S Haldane reported that genes which are linked, or on the same chromosome, are inherited together. From these early observations it was soon recognised that chromosomal segments are highly conserved over long periods of time and any changes in gene order can be used, along with other evidence (such as the fossil record), to chart the evolutionary history of a species. As the Human Genome Project has unfolded there have been enormous advances in DNA technologies. The development of PCR and automated sequencing especially have made it possible to construct genome maps with enough information to make them useful for comparative studies. Many mammalian genes have homologues in other animal groups. By comparing the amino acid sequences of the proteins coded for by these genes, or the DNA sequences themselves, it has become clear that many of the 70, ,000 genes within the mammalian genome have been conserved over hundreds of millions of years of independent evolution. Although we see a great variety in karyotypes, comparative mapping makes it clear that the order of genes as well as the sequences of those genes is highly conserved in mammals. Comparisons of human maps with those from other species provide clues into the evolutionary origin of regions of the genome. Although interesting in its own right this may also provide new insights into the function of these regions. As the initial stage of Human Genome Project nears its completion (with a completed DNA sequence expected by 2001), this will become increasingly important as scientists attempt to determine the meaning of the DNA sequences generated. Comparative genome maps made using genes and other DNA markers can be used to: predict the location of genes or markers in other species. If a new gene is mapped between two genes in one species, its homologue is probably located between the same two genes in another species. identify candidate disease genes. Disease causing genes mapped in model species (such as the mouse) have been used to locate the genes responsible for diseases such as Waardenburg Syndrome Type 1 and neurofibromatosis in humans. characterise the genetic basis for complex genetic traits. Although comparative maps are valuable for mapping single genes and identifying candidates for simple traits, they may be even more important for analysing complex traits such as those responsible for epilepsy, diabetes and hypertension. It is impossible to plan genetic crosses and control environmental factors in humans but this is possible in experimental species such as the laboratory mouse and rat with the added bonus of being able to produce large numbers of progeny. This approach is used to pinpoint regions of the genome important for complex traits. These regions can then be thoroughly investigated.

2 Worksheet - COMPARATIVE MAPPING 2 KEY TERMS linked genes human genome project PCR automated DNA sequencing genome maps karyotypes INSTRUCTIONS Genetic markers have been assigned to human and chicken chromosomes. By looking carefully at these markers: Either: Cut out human chromosomes 12 and 22 from the Chromosome Cut Out Sheet (H12 and H22) and paste the segments onto the answer sheet to make the chicken chromosomes 1 and 18 (C1 and C18). Or: Cut out chicken chromosomes 1 and 18 from the Chromosome Cut Out Sheet (C1 and C18) and paste the segments onto the answer sheet to make human chromosomes 12 and 22 (H12 and H22). Remember to leave out any extra centromeres because each chromosome should only have one centromere. Now answer the following questions: 1. Name the chromosomal mutations involved in the rearrangements you have just made. 2. Using the data provided is it possible to decide whether the chicken arrangement or the human arrangement is closer to that of their common ancestor? If not what other data do you need? 3. Now use the additional information provided on Chromosome sheet 2 to decide whether the chromosomal arrangement of the chicken or the human is more like the ancestral arrangement? Explain your answer. 4. You should now be able to complete the phylogenetic tree answer sheet.

3 C1 ITPR2 LDHB GAPD CHROMOSOME CUT OUT SHEET C18 H12 GAPD LDHB ITPR2 C1 - Chicken chromosome 1 C18 - Chicken chromosome 18 H12 - Human chromosome 12 H22 - Human chromosome 22 H22 Worksheet - COMPARATIVE MAPPING 3

4 Worksheet - COMPARATIVE MAPPING 4 C1 C18 ANSWER SHEET H12 H22

5 C1 ITPR2 LDHB GAPD C18 CHROMOSOME SHEET 2 H12 H22 D7 D7 - Dolphin chromosome 7 Worksheet - COMPARATIVE MAPPING 5

6 Worksheet - COMPARATIVE MAPPING 6 Phylogenetic tree - answer sheet ANCESTOR 300 mya 65 mya Present day Mya - million years ago

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