Genomics

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Genomics

• Biology 122
• Genes and Development

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Restriction analysis
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FISH
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Sequence-tagged sites (STS)
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Comparison of genetic and physical maps
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Manual sequencing
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Automated DNA sequencing
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Estimated genes in sequenced genomes
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Transposable elements
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Alternative splicing
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Comparison of plant genomes
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Neanderthals
Science Nov 17, 2006
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Neanderthals

• 99.5 identical to humans when comparing the same
  sequences

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Watsons genome

• Sequenced using shotgun sequencing
• About 3.5 percent of Watsons genome could not be
  matched to the reference genome-probably due to
  differences in cloning step

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Venters genome compared to the reference genome

• 32 million reads resulted in 2.8 billion base
  pairs of assembled sequence (7.5 fold coverage)
• 4.1 million differences to the already published
  genome (12.3 million bases different)
• 3,213,401 single nucleotide polymorphisms (SNPs),
  53,823 block substitutions (2-206 bp), 292,102
  heterozygous insertion/deletion events
  (indels)(1-571 bp), 559,473 homozygous indels
  (1-82,711 bp), 90 inversions, as well as numerous
  segmental duplications and copy number variation
  regions.

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How different are individuals?

• 44 of genes were heterozygous for one or more
  variants (they could determine both copies)
• A conservative estimate that a minimum of 0.5
  variation exists between two haploid genomes (all
  heterozygous bases).

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How different are individuals?

• DNA from a Yoruba from Ibadan, Nigeria was
  completed.
• About 4 million SNPs were found, 74 had already
  been found by others.
• About 24 more polymorphism (heterozygosity) than
  Caucasian genomes.
• There were 5,704 indels ranging from 50 to over
  35,000 bp long. Many were SINES and LINES.

Bentley et al., Nature, November 6, 2008
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How different are individuals?

• DNA from a Han Chinese individual was completed.
• About 3 million SNPs were found, 86 had already
  been found by others.
• About 24 more polymorphism (heterozygosity) than
  Caucasian genomes.
• There were 2,682 structural variations, including
  insertions, deletions, and inversions. Many
  variations in SINES and LINES were found.

Wang et al., Nature, November 6, 2008
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How different are cancer cells?

• DNA from skin cells and acute myeloid leukemia
  cells from the same Caucasian woman were
  sequenced.
• About 2.9 million SNPs were found in the skin
  cells, and 3.8 million in the leukemia cells.
• Almost all of the differences in SNPs were found
  to be common in other sequenced genomes or not in
  genes.
• Ten genes were found to have acquired mutations
  in the leukemia cells. Of these, two were known
  to be involved in tumour progression. The
  functions of the other eight mutant genes are
  unknown.

Ley et al., Nature, November 6, 2008
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Metabolomics

• A study of 284 males compared 383 metabolic
  indicators and SNPs (genetic variants).
• Up to 12 of the levels of the metabolic
  molecules could be explained by particular
  versions of the gene (SNP).
• Four genes were known to be in metabolic pathways
  related to the metabolic molecule that was high
  or low.

Geiger et al., PLOS Genetics. November, 2008
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Wooly mammoth

• Over 4 billion bp in genome
• Mammoths and African elephants differ in about 1
  amino acid per protein
• Estimate that Mammoths and African elephant
  separated 1.5 to 2.0 Million years ago

Nature, November 20, 2008
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Wooly mammoth
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Other mammals

• Peromyscus Peromyscus californicus
• Peromyscus Peromyscus leucopus
• Peromyscus Peromyscus maniculatus
• Peromyscus Peromyscus polionotus
• Alpaca Vicugna pacos
• Armadillo, Nine-Banded Dasypus novemcinctus
• Baboon Papio hamadryas
• Bonobo Bonobo Pan paniscus
• Bushbaby Otolemur garnetti
• Cat Felis catus
• Chimpanzee Chimpanzee Pan troglodytes
• Cow Bos taurusDog Canis familiaris
• Dolphin Tursiops truncates
• Elephant Shrew Elephantulus sp.
• Elephant, African Savannah Loxodonta africana
  Africana
• Ferret Ferret Mustela putorius furo
• Gibbon Gibbon Nomascus leucogenys
• Gibbon Nomascus lucogenys
• Guinea Pig Cavia porcellus

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Other mammals

• Hedgehog, European Erinaceus europeaus
• Horse Equus caballus
• Human Homo sapiens
• Hyrax Procavia capensis
• Kangaroo Rat Dipodomys sp.
• Lemur, Flying Dermoptera sp.
• Lemur, Mouse Microcebus murinus
• Little brown bat Myotis lucifugus
• Macaque, Rhesus Macaque Macaca mulatta
• Macaque, Cynomolgous Macaca fascicularis
• Macaque, Rhesus Macaque, Rhesus Macaca mulatta
• Marmoset Marmoset Callithrix jacchus
• Megabat Pteropus vampyrus
• Mole Cryptomys sp.
• Mouse Mouse Mus musculus
• Opossum, Laboratory Opossum, Laboratory
  Monodelphis domestica
• Orangutan Pongo pygmaeus
• Pangolin Manis pentadactyla
• Pika Ochotona princeps

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Other mammals

• Rabbit Oryctolagus cuniculus
• Rat Rattus norvegicus
• Shrew, European Common Sorex araneus
• Shrew, Tree Tupaia belangeri
• Sloth Choloepus hoffmanni
• Squirrel Spermophilis tridecemlineatus
• Squirrel Monkey Saimiri sp.
• Tarsier Tarsier syrichta
• Tenrec (Lesser Hedgehog) Echinops telfairi
• Vervet Vervet Chlorocebus aethiops
• Wallaby, Tammar Wallaby, Tammar Macropus eugenii
• Above data from Genome.gov, November 18, 2008
  update