Transcript 4. Gene350 Animal Genetics 30 July 2009

Gene350 Animal Genetics
Lecture 4
30 July 2009
Last Time
• Mendelian genetics
– Terminology
– Law of segregation
– Law of independent assortment
• Variations in dihybrid ratios
Today
• Study chromosomes
– The normal karyotypes of animals
– Chromosomal abnormalities
– Chromosomal abnormalities of animals
The normal karyotype of animals
Human, Homo
sapiens
23
Cat, Felis catus
19
Horse, Equus
caballus
32
Dog, Canis
familiaris
39
Pig, Sus scrofa
19
Mouse, Mus
musculus
20
Cattle, Bos
taurus
30
Rat, Rattus
norvegicus
21
Sheep, Ovis
aries
27
Chicken, Gallus
domestic
39
Rabbit
22
Donkey
31
Duck
40
Turkey
40
Goat
30
Variations in Chromosome
Number and Arrangement
• Chromosomal mutations or aberrations
– Abnormal chromosomal number
– Gene deletion or duplication
– Chromosome rearrangements
• Aberrant chromosomes passed on in a
Mendelian fashion
Terminology
• Euploid – chromosomes present in complete
haploid units
– Haploid
– Diploid
– Triploid
– Tetraploid
• Aneuploid – loss or gain of one or more
chromosomes
• Alloploid – multiples of different genomes
Aneuploidy
• Commonly results from nondisjunction during
meiosis
– Monosomy, trisomy, tetrasomy, etc.
– Klinefelter and Turner syndromes are examples
involving human sex chromosomes
Nondisjunction
Monosomy
• 2n – 1 condition
• Monosomy involving autosomes may have severe
phenotypic effects in animal species (but
generally not plants)
– Monosomy for Drosophila chromosome 4 (only 5% of
genome) gives live fly but small and with low viability
– Monosomy for chromosomes 2 and 3 lethal
• Issues
– Gene dosage effects
– Expression of all encoded recessive alleles
Trisomy
• Trisomy (2n + 1)
– Somewhat/slightly less severe than monosomy
when involves autosome
– Large autosomes usually lethal in both Drosophila
and humans
• Generally viable in plants
• Meiotic issues
– Trivalents form by synapsing
– Anaphase has one going to one cell, two to the
other
Trisomy Meiosis
Down Syndrome
•
•
•
•
•
Discovered in 1866 by John Langdon Down
Now known to result from trisomy 21 (47 +21)
One per 800 live births
75% due to nondisjunction in meiosis I
Ovum is source of extra 21 in 95% of cases
– Maternal age
• Ova can be stalled in meiosis I for 20 or more years…
• Familial Down syndrome is the result of a translocation of
a portion of chromosome 21
Down Syndrome – Trisomy 21
Maternal Age
and Down
Syndrome
• 1/1000
births when
maternal
age is 30
• 1/100 at
age 40
• 1/50 at age
50
Chromosome Rearrangements
• Types
– Deletions
– Duplications
– Translocations
• Reciprocal
• Nonreciprocal
• Most involve one or more breaks in the
DNA/chromosome
– Broken ends lack telomeres and can be “sticky”
• Can rejoin with other ends
Consequences of Rearrangements
• Are heritable to daughter cells
– And if in germ line to subsequent generations
• Balanced translocations may not impact
individual greatly
– But gamete production will create defective
cells/zygotes with predictable frequency
• Gene dosage
• Pairing problems during meiosis
Deletions
• Deletions
– Terminal deletions remove end of chromosome
• Often a result of DNA damage involving strand breakage
– Intercalary deletions delete an interior portion
• Only portion retaining centromere will be maintained in
daughter cells
• Synapsing with normal chromosome creates a deletion
loop or compensation loop visible during meiosis
• Crossover between direct repeats can result in an internal
deletion
Compensation Loop in a Polytene
Chromosome
• Create partially
hemizygous
condition and
result in
phenomenon
called
pseudodominance
Duplications
• Section of chromosome occurs more than
once in a haploid equivalent (genome)
– Commonly arise from unequal crossing over
– Important evolutionary process
Unequal Crossing Over
Unequal Crossing Over
• Creates gene redundancy/amplification
– Allows for high level expression
– Particularly useful for some structural RNA genes
• rRNA genes (rDNA)
– About 5-10 copies per bacterial genome
– About 130 copies/ Drosophila genome
• Loss of copies leads to abnormal phenotype
– Xenopus has about 400 copies/genome
• But the oocyte may have up to 1500 micronuclei (each
with an NOR) to give up to 600,000 copies of rDNA
Position Effects
• Gene
dosage not
everything
• Bar-eye
phenotype
in
Drosophila
Gene Duplication and Evolution
• 1970 Susomo Ohno – “Evolution by Gene
Duplication”
– Gene duplication produces a reservoir of genes
from which to evolve new ones
• Why reinvent the wheel from scratch?
• Gene families
– Immunoglobulin, T-cell receptor and MHC
families make up a super family
• For fifty single copy genes in Drosophila,
have multiple copies in humans
Gene Duplication and Evolution
• Yeast genome has about 5000 genes with about
55 duplicated regions that encode 376 pairs of
duplicated genes
• Humans have 1077 duplicated blocks of genes,
with 781 having 5 or more copies of the
duplicated segment
– Make up nearly half of chromosomes 18 and 20
Chromosomal Inversions
• No loss of genetic information (nucleotides)
• Crossover between inverted repeats
• Segment is inverted 180 degrees in chromosome
Chromosomal Inversions
• Paracentric inversion does not involve centromere
• Pericentric inversion involves centromeric region
Inversions and
Gametogenesis
• One member of
homologous pair has
inversion
– Normal pairing during
meiosis not possible
• Inversion loop forms
• When no recombination
occurs, 50% of gametes
have inversion
– But recombination can
occur…
Inversions and Gametogenesis
• Can break genes
• May cause position effects
– Especially if transported to position near heterochromatin (white
eye in Drosophila moved to near centromere)
• Major problems with recombination
• Meiosis/mitosis
– Acentric chromosomes – no centromere
– Dicentric chromosomes – two centromeres
• On the plus side…
– Inversions can stabilize a good combination of alleles by blocking
crossovers that would separate them
Inversions and
Recombination
• Many defective gametes
can be produced
• Can be “adaptive” when it
stabilizes a superior
combination of alleles on a
chromosome
– Examples seen in Drosophila
Translocations
• Reciprocal
translocations result
from crossover events
between
nonhomologous
chromosomes
– Balanced translocation
condition may result
• Semisterility (50%)
Familial Down Syndrome
• Robertsonian translocation
or centric fusion
– Fusion of the Q arms of two
acrocentric chromosomes
(13,14, 15, 21 and 22)
– P arms lost (no centromeres)
Familial Down
Syndrome
• Most of Q arm from
chromosome 21
translocated to 14
(14/21
translocation)
• Fusion occurs at two
rDNA regions on the
chromosomes
– About 20% rDNA
copies lost
– Carrier still normal