Homework #2 is due now Bonus #1 is due 10/24

deogr[Xpter:Xqter],genes[1.00: ] Fig Map of human chromosome 20 How does the organization of a genome affect its function?

Some genes have several similar sequences within the genome: known as a gene family

Hemoglobin (carries O 2 in the blood) is comprised of a gene family in humans

Different members of the hemoglobin gene family are expressed at different developmental stages Fig 19.17

Fetal Hb binds O 2 more strongly than maternal Hb

Pseudogenes have the structure of a gene, but are not expressed. Fig 19.18

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78: and Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23:

Transposons: mobile DNA

Transposons comprise much of human DNA From “Biology 7th ed.” by Campbell et al fig 19.14

Fig Retro- transposons move via an RNA intermediate

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Humans and chimpanzees shared a common ancestor about 6 million years ago

human chimp Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Tbl 2 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Fig 1 Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23:

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity What affect do transposons have in humans?

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Tbl 1 Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23: Does transposition cause disease?

The coding capacity of L1 was not fully recognized until an active copy with intact ORFs ‘jumped’ into the factor VIII gene and caused hemophilia.

Diseases caused by transposon insertion: Duchenne muscular dystrophy Coffin-Lowry syndrome Fukuyama-type congenital muscular dystrophy (FCMD) colon cancer chronic granulomatous disease X-linked dilated cardiomyopathy familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism neurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10–100 live births Which transposons are mobile?

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans. For example, over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans.

Tbl 1 Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23: Which transposons are mobile?

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity Transposons are still active, and can cause mutations and disease.