Chapter Introduction

359

17

key concepts

17.1

Genomes Can Be Sequenced Rapidly

17.2

Prokaryotic Genomes Are Compact

17.3

Eukaryotic Genomes Contain Many Types of Sequences

17.4

Human Biology Is Revealed through the Genome

17.5

Proteomics and Metabolomics Can Provide Insights beyond the Genome

Genomes

PART FIVE Genomes

image
Genome sequencing has revealed insights into how size is controlled by genes.

investigating life

The Dog Genome Project

Canis lupus familiaris, the dog, was domesticated by humans thousands of years ago. While there are many kinds of wolves, they all look about the same. Not so with “man’s best friend.” The American Kennel Club recognizes about 155 different breeds, which not only look different but also vary greatly in size. For example, an adult Chihuahua weighs just 1.5 kg, whereas a Scottish deerhound weighs 70 kg. No other mammal shows such large phenotypic variation. Also, there are hundreds of genetic diseases in dogs, many of which have counterparts in humans. To study the genes behind the phenotypic variation, and to elucidate the relationships between genes and diseases, the Dog Genome Project was started in the late 1990s.

Two dogs—a boxer and a poodle—were the first to have their entire genomes sequenced. The dog genome contains 2.8 billion base pairs of DNA in 39 pairs of chromosomes. There are 19,000 protein-coding genes, most with close counterparts in other mammals, including humans. Given the whole genome sequence, researchers began to map genetic markers—specific nucleotides or short sequences of DNA—at particular locations on the genome that differ among individual dogs or breeds.

Genetic markers can map the locations of (and thus identify) genes that control particular traits. For example, Dr. Elaine Ostrander and her colleagues at the National Institutes of Health studied Portuguese water dogs to identify genes that control size. Samples of cells for DNA isolation were obtained by sweeping a cotton swab over the inside of the cheek. It turned out that the gene for insulin-like growth factor 1 (IGF-1) is important in determining size: large breeds have an allele that codes for an active IGF-1, and small breeds have a different allele that codes for a less active IGF-1.

Inevitably, some scientists set up companies to test dogs for genetic variations, using DNA supplied by people anxious to validate the “purebred” status of their dogs. Not to be outdone, cat fanciers have sequenced the genomes of domestic and wild cats. Comparisons of these animal genomes help establish the evolutionary history of mammalian lineages as well as identify the genes responsible for diseases and traits seen in various mammalian species.

Question

What have we learned from sequencing animal genomes?