Download Genomics 1 The Genome

Genomics
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The Genome
The cattle genome consists of 30 pairs of chromosomes which are made of DNA. The are
at least 3.5 billion base pairs within the DNA of those 30 chromosomes. Amino acids
are coded by 3 bases, like TAA or TGC. A set of amino acids codes for a protein or
enzyme which influences activities within the body of an individual. Only about 5% of
the genome actually codes for proteins and enzymes, with the remaining 95% seeming to
be redundant. The purpose of the extraneous DNA is unknown, but some areas are highly
conserved and similar between species, and thus, could be DNA that was once important
in evolution to the present day. Another hypothesis is that the extra DNA is involved in
the timing of the activation and shut-off of the coding regions of DNA. The purpose of
DNA of all types is being studied actively today with almost weekly articles in newspapers
and magazines about new mysteries of the DNA. This area will play an important role in
your future lives, and it is both very interesting and probably very critical to your futures.
From one individual to the next there are variations in the sequences of base pairs.
Variations can be due to
1. A change in one base pair, where A changes to G, or G changes to C,
2. A few base pairs are missing between animals,
3. A few extra base pairs are added between two animals, or
4. The order of the base pairs can be inverted or moved to a different part of the
chromosome.
Depending on the location of the variations in the genome, there could be different effects
on the animal. Some variations (if they are in non-coding regions, for example) may not
cause any change in the proteins and enzymes that are produced. Some variations may
be in coding regions of the genome, but may still be harmless and result in no changes
in functioning. Some variations could cause changes, such as in height of individuals or
colour of the eyes or hair, which are also harmless. Finally, variations could be harmful
and cause serious and even lethal changes in the individual due to an inability to produce
the correct series of amino acids.
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Single Nucleotide Polymorphism, SNP
The most abundant type of variation in human and cattle genomes is the single nucleotide
polymorphism or SNP, where a single base pair has been changed. To be called a SNP,
at least 1% of the population must have the different base change. To find SNP, one
must start at one end of the genome and go through it base by base comparing between
two individuals (Sequence Comparisons). SNPs are discovered by comparing individuals
that are greatly different in background - such as different breeds, or very high producers
versus very low producers.
Millions of SNPs have been found in humans, and there are over 800,000 in cattle
with more being discovered every day. Some of the same SNPs appear in both humans
and cattle. In 2003, a company called Affymetrix (California) produced a ’chip’ or ’panel’
or ’array’ of 10,000 SNP (from human studies). A DNA sample is put on the chip, and
the genotypes of the animal for 10,000 SNP could be determined for a cost of about $350
per animal.
The goal of a USDA-dairy industry project started in 2006 was to discover Quantitative Trait Loci (i.e. genes) that had large, significant effects on various traits in cattle.
Researchers went through all of the available known SNPs in cattle and deliberately chose
which SNPs to be on the panel. The result was the Illumina 50K chip. DNA for the study
was collected from semen samples from over 5,000 dairy and beef bulls from North America, including Canada. In 2010, Illumina is developing a SNP chip with 800,000 SNPs.
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Genome Wide Selection
For each SNP locus there are just 3 possible genotypes. In 2001, Meuwissen, Hayes, and
Goddard published a paper that showed if the SNPs were evenly spread through the
genome, then it was possible to estimate the effects of genotypes at each SNP locus on a
trait of interest. The estimates could be put into a table as follows:
Genotype Locus 1 Locus 2
11
0.10
3.60
12
0.50
4.58
22
0.90
5.63
Locus 3 · · ·
10.97
12.44 · · ·
15.33
Locus n
-1.12
-3.56
-5.87
There would be genotype estimates for every SNP locus. Thus, if a 50K chip was
used, there would be 50,000 genotypes for one animal. A Genomic Estimated Breeding
Value (GEBV), could be constructed from the table of genotype estimates. Suppose the
genotypes of animal X were (11, 12, 22, · · · , 12), then the animal’s GEBV would be the
sum of (0.10 + 4.58 + 15.33 + · · · -3.56) = 48.72, for example. Given the genotypes, sum
the corresponding genotype estimates together for all SNP loci.
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According the Meuwissen et al. (2001) the correlation between GEBV and an animal’s
true breeding value (TBV) would be as high as 0.85 or better. There estimate was based on
simulation work in which many assumptions were made. In practice, so far, a correlation
of 0.6 to 0.7 is probably the best that can be done. This is slightly more accurate than
using a Parent Average EBV.
All animals with the same parents would receive the same Parent Average EBV as
an estimate of their genetic merit. However, with a GEBV, each offspring would have
a different GEBV because their genotypes would most likely be different. Thus, GEBV
would allow the best offspring of a sire and dam to be chosen.
Since the early work of Meuwissen et al. (2001) others have proposed different methods of computing GEBV for individuals. As of August 2008 the best method has not yet
been found.
An advantage of GEBV is that an animal can be genotyped at birth and a GEBV
can be calculated with an acceptable accuracy. There is no need to wait until the animal
is mature, or until the animal has some progeny, to select or cull that animal based on
its genetic merit. The generation interval can be reduced. How this would work in dairy
cattle was described by Schaeffer (2006), where genetic change could be doubled, and the
cost of progeny testing could be reduced by two thirds or more. Also, fewer bulls would
be needed.
Two countries have started to make use of GEBV. They are New Zealand and the
Netherlands. France and Canada have been selecting bulls for progeny testing on the basis
of genotypes for 14 or so markers (not 50,000). In 2009, the USDA will publish GEBV
(combined with usual EBVs). Thus, the era of Genome Wide Selection is beginning.
There will be significant changes in the dairy industry in the next few years because
of this technology. The effect of GEBV on the increase in inbreeding will need to be
monitored and controlled.
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Future?
In humans, it is possible to have one’s entire genome sequenced, so that the order of
the 3 billion base pairs is known. With this information, the sequences of known genetic
disorders can be “matched” to your genome to see if they are present or not. Thus, you
will know which diseases you may incur in your life, and therefore, you might be able to
alter your lifestyle to prevent the disease from occurring.
The SNP era will eventually be replaced by the era of complete genome sequencing.
There will be billions of base pairs of information available on every human and every
breeding animal, and use of this information will be made to help humans with diseases,
and to choose animals for breeding. The problems will be 1) the storage of this quantity
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of information; 2) the manipulation of this data to be useful; and 3) the discovery of
genes and their functions. Bioinformatics will be a huge area needing many thousands
of workers in the future. People will be needed for computing, statistics, genetics, and
proteomics (study of proteins and gene functions).
REFERENCES
Meuwissen, T. H. E., B. J. Hayes, M. E. Goddard. 2001. Prediction of total genetic
value using genome-wide dense marker maps. Genetics 157:1819-1829.
Schaeffer, L. R. 2006. Strategy for applying genome-wide selection in dairy cattle. J.
Anim. Breed. Genet. 123:1-6.
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