Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

Chapter 2
Comparative Medical Genetics
Petra Werner
Department of Clinical Studies
Section of Medical Genetics
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Mark Haskins
Department of Pathology
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Urs Giger
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
I. INTRODUCTION
A. Genome Sequences
B. Mapping the Genome
C. Disease Gene Mapping
D. Genetic Diseases
E. Gene Therapy
REFERENCES
I . INTRODUCTION
A . Genome Sequences
All the genetic information needed for the creation, maintenance,
and reproduction of an organism is called the
genome. For most organisms, this information is encoded in
the DNA (deoxyribonucleic acid) or for some viruses in the
RNA. A first step in the gigantic endeavor to understand this
genetic information is to learn about the complete nucleotide
sequence of a genome. Such genome projects have
been or will be undertaken for many different organisms.
The progress made with the Human Genome Project
around the turn of the century has not only produced an
extraordinary resource for genetic research in human
medicine, but it has also created the means for sequencing
additional genomes. Following the completion of the
high-density human genome sequence, these tools and
sequencing capacities have been used for a variety of species,
starting with that of model organisms. The mouse, as
one of the most relevant models for genetic research, was
the second mammal to be sequenced; however, genome
sequences from rat, fruit fly, and zebra fish were soon to
follow. The next group of genomes included those of
domestic animals, such as the dog, cow, chicken, and
pig, which were chosen because they also serve as model
organisms and are of special interest as either companion
or food animals. Genomes of other animals, including cat
and horse, were chosen to help with the annotation of the
human and other mammalian genomes (comparative annotation).
They were sequenced at lower genome coverage
and are expected to provide important information about
genome evolution. Alignment and comparison of the available
animal genomes to the human will help identify evolutionarily
conserved regions, which mostly likely represent
important functional elements. This is a critical step for
the annotation of the human and animal genomes and the
understanding of genomic function. Completed genome
sequences for several domestic animals are now available
( Table 2-1 ) and semiannual updates on the status of current
sequencing projects are listed on the National Institutes of
Health (NIH) website ( www.genome.gov/10002154 ).
Many aspects of the canine genome and its impact
on comparative and medical genetics are covered in The
Dog and Its Genome (Ostander et al. , 2006). The knowledge
about the genomes of companion animals will have
an enormous impact on veterinary medicine by facilitating
the identification of genes underlying breed characteristics
including behavior, coat color, body type, disease predispositions,
and the detection of disease-causing mutations.
This knowledge will lead to great advances in genetic
screening for desirable and disease-causing traits as well as
breed-specific vaccine and drug development (custom drug
design). It will also change livestock breeding and production
through identification of productivity and diseaseresistance
genes.
B . Mapping the Genome
The nuclear genome is composed of a species-specific
number of linear DNA molecules, which are packaged into
chromosomes. The number of chromosomes varies greatly
among eukaryotes (for haploid chromosome numbers,
see Table 2-1 ) but appears to be unrelated to genome size
and its biological features. During cell division, DNA is
Clinical Biochemistry of Domestic Animals, 6th Edition 27
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