1. Chromosome Basis of Inheritance

2. Genetic Information
Gene – basic unit of genetic information. Genes determine the inherited characters.
Genome – the collection of genetic information.
Chromosomes – storage units of genes.
DNA - is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life

3. Human Genome Most human cells contain 46 chromosomes
2 sex chromosomes (X,Y):
XY – in males.
XX – in females.
22 pairs of chromosomes named autosomes.

4. Chromosome Theory of Inheritance
Genes have specific locations (loci) on chromosomes.
It is the chromosome that segregates and assorts independently.
How does this relate to Mendel’s laws of inheritance?

5. What is the difference between an Autosome and a Sex-chromosome?
Autosomes are the first 22 homologous pairs of human chromosomes that do not influence the sex of an individual.
Sex Chromosomes are the 23rd pair of chromosomes that determine the sex of an individual.

6. Autosomal Traits
Genes located on Autosomes control Autosomal traits and disorders.
2 Types of Traits:
Autosomal Dominant
Autosomal Recessive

7. Sex Linked Genes in Humans
Characteristics that are inherited from genes found on the sex chromosomes
Normally on the X chromosome as the Y chromosome is small and has very few genes.
Most seX-linked traits are recessive
More common in males than females
Males only needs to inherit one sex-linked recessive allele from mom to be expressed
Females has to inherit two sex-linked recessive alleles for expression
Examples
Red-green color blindness
Hemophilia

8. Sex Linked Traits X-linked recessive, carrier mother
Unaffected
son
daughter
Affected
Carrier
father
mother
It is possible for a female to be a carrier of an X-linked trait, but not express it
SRY gene: gene on Y chromosome that triggers the development of testes
Fathers= pass X-linked alleles to all daughters only (but not to sons
Mothers= pass X-linked alleles to both sons & daughters
Men will express all X- linked traits they inherit

9. Discovery of Sex-Linked Genes
Thomas Hunt Morgan in The Fly Room! (Columbia University 1910)
Fruit Flies (Drosophila melanogaster)
© 2007 Paul Billiet ODWS

10. Chromosomal Linkage Thomas Hunt Morgan Drosophilia melanogaster
XX (female) vs. XY (male)
Sex-linkage: genes located on a sex chromosome
Linked genes: genes located on the same chromosome that tend to be inherited together

11. Sex-Linked Recessive Pedigree
Draw a Pedigree showing a cross between a Red eyed Male fruit fly and a Carrier Female fruit fly which have 2 males and 2 females. (Show all possibilities) Red is dominant to white.
Genotypes of Parents:
Male = XR Y Female = XR Xr
XRY
XRXr
XrY
XRXR

12. Rules for Sex-Linked Recessive Traits
More males than females are affected.
An affected son can have parents who have the normal phenotype. (XAY x XAXa)
For a daughter to have the trait, her father must also have it. Her mother must have it or be a carrier (XaY, XaXa, XAXa)
The trait often skips a generation from the grandfather to the grandson.
If a woman has the trait (XaXa), all of her sons will be affected.
Pedigrees show only female carriers but no male carriers.

13. Examples of Sex-Linked Recessive Disorders
Red/Green Colorblindness – Difficulty perceiving differences between colors (red or green, blue or yellow).
Hemophilia – Absence of one or more proteins necessary for normal blood clotting.
Deafness
Cataracts – opacity in the lens that can lead to blindness
Night blindness – (Nyctalopia) rods do not work so that can not see in the dark
Glaucoma – pressure in the eye that can lead to optic nerve damage and blindness
Duchenne Muscular Dystrophy – progressive weakness and degeneration of skeletal muscles that control movement due to absence of dystrophin (protein that maintains muscle integrity). Mainly in boys, onset 3-5 yrs, by 12 years can’t walk, and later needs respirator.

14. X- Inactivation
X-inactivation is a process by which one of the two copies of the X chromosome present in female mammals is inactivated (methylation)
X-inactivation occurs so that the female with two X chromosomes does not have twice as many X chromosome gene products as the male, which only has a single copy of the X chromosome
Inactivation is random
The coloration of tortoiseshell cats is a visible manifestation of X inactivation. The black and orange alleles of fur color are on the X chromosome. For any given patch of fur the inactivation of an X chromosome that carries one gene results in the fur color of the other active gene.

15. X- Inactivation Barr Bodies
The inactive chromosome condenses into a Barr body, which lies along the inside of the nuclear envelope
In men and women with more than one X chromosome, the number of Barr bodies visible at interphase is always one less than the total number of X chromosomes. For example, men with a 47,XXY karyotype have a single Barr body, whereas women with a 47, XXX karyotype have two Barr bodies

16. GENE LINKAGE Genes are located on the same chromosome
Alleles cannot separate according to the laws of Independent Assortment and Random Segregation
Unless…crossing over during meiosis I moves them to a different chromosome.
We measure the distance between genes by the frequency of crossing over moving one of them to a new chromosome, called gene linkage mapping
Distant genes are separated by crossing over more often than nearby genes.

17. Genetic Recombination
Results in offspring with a new combination of genes inherited from the parents
Parental Type
Some offspring will have same phenotype as one of the parentslaws of Independent Assortment and Random Segregation
Recombinants
Some offspring will have phenotypes different from both parents

18. gene linkage C is farther away from A than B is
We figure this out because a higher percentage of gametes are ABc than are Abc.
In fruit flies, wings and body color are linked

19. Linkage Map
Genetic map that is based on the percentage of cross-over events
A map unit is equal to a 1% recombination frequency.
Map units are used to express relative distances along the chromosome.

20. Genetic recombination Summary
Crossing over
Genes that DO NOT assort independently of each other
Genetic map
The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency
Linkage maps
Genetic map based on recombination frequencies

21. Chromosomal Mutations
Damage to chromosomes due to physical or chemical disturbances or errors during meiosis.
Two Types of Chromosome Mutations:
Chromosome Structure
Chromosome Number

22. Problems with Chromosome Structure:
Deletion – during cell division, especially meiosis, a piece of the chromosome breaks off, may be an end piece or a middle piece (when two breaks in a chromosome occur).
Inversion – a segment of the chromosome is turned 180°, same gene but opposite position
Translocation – movement of a chromosome segment from one chromosome to a non-homologous chromosome
Duplication – a doubling of a chromosome segment because of attaching a broken piece form a homologous chromosome, or by unequal crossing over.

23. Structural Errors

24. Problems with Chromosome Number
Nondisjunction
When members of a pair of homologous chromosomes do not separate properly during meiosis I
Sister chromatids don’t separate properly during meiosis II

25. Chromosomal Mutations
Monosomy and Trisomy due to Nondisjunction
members of homologous chromosomes do not move apart in Meiosis I or sister chromatids do not separate during Meiosis II leaves one cell with too few chromosomes and one cell with too many.
Triploids develop from the fertilization of an abnormal diploid egg, produced from the nondisjunction of all chromosomes.
Tetraploids develop from the failure of a 2n zygote to divide after replicating its chromosomes, subsequent mitosis would produce 4n embryo.

26. Chromosomal Mutations
Polyploidy is common in the plant kingdom, spontaneous origin of polyploid individuals plays important role in evolution of plants.
In the animal kingdom, natural occurrence of polyploids is extremely rare.
In general, polyploids are more nearly normal in appearance than having monosomy or trisomy, which is more disruptive to have one extra chromosome in a pair.

27. Summary
Nondisjunction: members of a pair of homologous chromosomes do not separate properly during meiosis I or sister chromatids fail to separate during meiosis II
Aneuploidy: chromosome number is abnormal • Monosomy~ missing chromosome • Trisomy ~ extra chromosome (Down syndrome) • Polyploidy~ extra sets of chromosomes

28. Genomic imprinting
Genonmic imprinting is a parental effect on gene expression
Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm.
Fragile X syndrome: higher prevalence of disorder and retardation in males

29. Trisomy 21 Trisomy 21 is the presence of 3 chromosome 21’s.
Condition is called Down Syndrome
Characteristics are specific and familiar but not all individuals show the exact same characteristics.

30. Down Syndrome
Individuals with Down syndrome have a typical facial appearance
All have some degree of mental retardation, but for most it is mild to moderate.
Can learn to read, write, do some math, and live day-to-day with minimal assistance.
Others require a lot of attention and care

31. Down Syndrome
There are several possible health concerns, including heart problems and hearing loss.
Individuals are now living longer than in the past, into their 50’s and 60’s
We are now discovering that those individuals who survive to this age are at very high risk for developing Alzheimer’s disease

33. Klinefelter Syndrome
People with this disorder develop as males with subtle characteristics that become apparent during puberty.
Often tall and usually don't develop secondary sex characteristics, such as facial hair or underarm and pubic hair.
Different distribution of body fat, more than usual in the chest and hips.
May have some degree of mental retardation.
Some individuals are never diagnosed.

34. Klinefelter Syndrome Affects about 1 in 1000 males
The extra X chromosome primarily affects the testes, the most common feature being infertility
2% of infertile men are diagnosed with Klinefelter syndrome

36. Turner Syndrome Affects about 1 in 5000 newborn girls.
Estrogen and other growth hormones are not produced in sufficient quantity.
When caught in infancy, TS can be managed and treated with regular medical care.

37. Turner Syndrome
Females with Turner are shorter than average and can have other noticeable physical features.
Broad chest, swelling in hands and feet, webbed neck.
Other health issues can include heart disease, horseshoe shaped kidneys, learning disabilities