1. Gene350 Animal Genetics
Lecture 4
30 July 2009

2. Last Time Mendelian genetics Variations in dihybrid ratios Terminology
Law of segregation
Law of independent assortment
Variations in dihybrid ratios

3. Today Study chromosomes The normal karyotypes of animals
Chromosomal abnormalities
Chromosomal abnormalities of animals

4. The normal karyotype of animals
Human, Homo sapiens 23
Cat, Felis catus 19
Horse, Equus caballus 32
Dog, Canis familiaris 39
Pig, Sus scrofa
Mouse, Mus musculus 20
Cattle, Bos taurus 30
Rat, Rattus norvegicus 21
Sheep, Ovis aries 27
Chicken, Gallus domestic
Rabbit 22
Donkey 31
Duck 40
Turkey
Goat

5. 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

6. Terminology Euploid – chromosomes present in complete haploid units
Diploid
Triploid
Tetraploid
Aneuploid – loss or gain of one or more chromosomes
Alloploid – multiples of different genomes

8. Aneuploidy Commonly results from nondisjunction during meiosis
Monosomy, trisomy, tetrasomy, etc.
Klinefelter and Turner syndromes are examples involving human sex chromosomes

9. Nondisjunction

10. 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

11. Trisomy Trisomy (2n + 1) Meiotic issues
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

12. Trisomy Meiosis

13. 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

14. Down Syndrome – Trisomy 21

15. Maternal Age and Down Syndrome
1/1000 births when maternal age is 30
1/100 at age 40
1/50 at age 50

16. 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

18. 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

19. 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

21. Compensation Loop in a Polytene Chromosome
Create partially hemizygous condition and result in phenomenon called pseudodominance

22. Duplications
Section of chromosome occurs more than once in a haploid equivalent (genome)
Commonly arise from unequal crossing over
Important evolutionary process

23. Unequal Crossing Over

24. 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

25. Position Effects Gene dosage not everything
Bar-eye phenotype in Drosophila

26. 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

27. 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

28. Chromosomal Inversions
No loss of genetic information (nucleotides)
Crossover between inverted repeats
Segment is inverted 180 degrees in chromosome

29. Chromosomal Inversions
Paracentric inversion does not involve centromere
Pericentric inversion involves centromeric region

30. 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…

31. 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

32. 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

33. Translocations
Reciprocal translocations result from crossover events between nonhomologous chromosomes
Balanced translocation condition may result
Semisterility (50%)

34. 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)

35. 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