1. Chapter 15~ The Chromosomal Basis of Inheritance

2. The Chromosomal Theory of Inheritance
Genes have specific loci on chromosomes and chromosomes undergo segregation and independent assortment

3. Chromosomal Linkage XX (female) vs. XY (male)
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

4. Classes of chromosomes
autosomal chromosomes
sex chromosomes

5. Discovery of sex linkage
true-breeding
red-eye female
true-breeding
white-eye male X P
Huh! Sex matters?!
100%
red eye offspring F1
generation
(hybrids)
100%
red-eye female
50% red-eye male
50% white eye male F2
generation

6. What’s up with Morgan’s flies?x x RR rr Rr Rr r r R r R Rr Rr R RR Rr R Rr Rr r Rr rr
100% red eyes
3 red : 1 white

7. Genetics of Sex X Y X XX XY X XX XY
In humans & other mammals, there are 2 sex chromosomes: X & Y
2 X chromosomes
develop as a female: XX
gene redundancy, like autosomal chromosomes
an X & Y chromosome
develop as a male: XY
no redundancy X Y X XX XY X XX XY
50% female : 50% male

8. Let’s reconsider Morgan’s flies…x x
XRXR
XrY
XRXr
XRY Xr Y XR Y XR XR
XRXr
XRY
XRXR
XRY XR Xr
XRXr
XRY
XRXr
XrY
100% red females
50% red males; 50% white males
100% red eyes

9. Genetic Recombination
Results in offspring with new combinations of traits inherited from their parents
Unlinked Genes:
Parental (phenotype like one of parents)
Recombinant (phenotype unlike either parent)
Linked Genes:
Do not assort independently
Too close on chromosome
Tend to be inherited together

10. Genetic recombination
Crossing over: Exchange of genetic material (Prophase 1)
Genetic maps: The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency. 1 map unit = 1% recombination
Linkage maps: Genetic map based on recombination frequencies
Helps you determine location of genes on chromosomes

11. Create a Linkage Map
A  B 10%
B  C 4%
A C 6%

12. Genes on sex chromosomes
Y chromosome
few genes other than SRY
sex-determining region
master regulator for maleness
turns on genes for production of male hormones
many effects = pleiotropy!
X chromosome
other genes/traits beyond sex determination
mutations:
more common in males
Color-blindness – lack of photopigments in eye
Duchenne muscular dystropy (MD) – lack of muscle protein
Hemophilia – lack of blood clotting protein
Fathers= pass X-linked alleles to all daughters only (but not to sons)
Mothers= pass X-linked alleles to both sons & daughters
Duchenne muscular dystrophy affects one in 3,500 males born in the United States.
Affected individuals rarely live past their early 20s.
This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin.
The disease is characterized by a progressive weakening of the muscles and loss of coordination.

14. Hemophilia XHXh XHY Hh x HH XH XHXh XH Y Xh XHXH XHXH XHY XHY XH Xh XH
sex-linked recessive
Hemophilia
XHXh
XHY
Hh x HH XH
XHXh XH Y
male / sperm Xh
XHXH
XHXH
XHY
XHY XH Xh
female / eggs XH
XHY
XHXh
XHXh
XhY
XhY Y
carrier
disease

15. X-inactivation Female mammals inherit 2 X chromosomes XH XHXh Xh
one X becomes inactivated during embryonic development
condenses into compact object = Barr body
which X becomes Barr body is random
patchwork trait = “mosaic”
patches of black
XH
XHXh
Xh
tricolor cats can only be female
patches of orange

16. Chromosomal Abnormalities
Errors of Meiosis
Chromosomal Abnormalities

17. Chromosomal abnormalities
Incorrect number of chromosomes
nondisjunction
chromosomes don’t separate properly during meiosis
breakage of chromosomes
deletion
duplication
inversion
translocation

18. Nondisjunction
Problems with meiotic spindle cause errors in daughter cells
homologous chromosomes do not separate properly during Meiosis 1
sister chromatids fail to separate during Meiosis 2
too many or too few chromosomes 2n
n-1 n
n+1

19. Alteration of chromosome number
error in Meiosis 1
error in Meiosis 2
all with incorrect number
1/2 with incorrect number

20. Nondisjunction Baby has wrong chromosome number~ aneuploidy trisomy
cells have 3 copies of a chromosome
monosomy
cells have only 1 copy of a chromosome
n+1 n
n-1 n
trisomy
2n+1
monosomy
2n-1

21. Polyploidy
Chromosomal alteration in which an organism has more than 2 complete chromosome sets
Triploid (3n)
Tetraploid (4n)
Common in plants

22. Down syndrome
Trisomy 21
3 copies of chromosome 21
1 in 700 children born in U.S.
Chromosome 21 is the smallest human chromosome
but still severe effects
Frequency of Down syndrome correlates with the age of the mother
Trisomy 13 occurs in about 1 out of every 5,000 live births. It is a syndrome with multiple abnormalities, many of which are not compatible with life. More than 80% of children with trisomy 13 die in the first month. Trisomy 13 is associated with multiple abnormalities, including defects of the brain that lead to seizures, apnea, deafness, and eye abnormalities. The eyes are small with defects in the iris (coloboma ). Most infants have a cleft lip and cleft palate, and low-set ears. Congenital heart disease is present in approximately 80% of affected infants. Hernias and genital abnormalities are common.
Trisomy 18 is a relatively common syndrome affecting approximately 1 out of 3,000 live births, and affecting girls more than three times as often as boys. The presence of an extra number 18 chromosome leads to multiple abnormalities. Many of these abnormalities make it hard for infants to live longer than a few months.
The cri du chat syndrome is caused by the deletion of information on chromosome 5. It is likely that multiple genes on chromosome 5 are deleted. One deleted gene, called TERT (telomerase reverse transcriptase) is involved in control of cell growth, and may play a role in how some of the features of cri cu chat develop. The cause of this rare chromosomal deletion is not known, but it is expected that the majority of cases are due to spontaneous loss of a piece of chromosome 5 during development of an egg or sperm. A minority of cases result from one parent carrying a rearrangement of chromosome 5 called a translocation. Between 1 in 20,000 and 1 in 50,000 babies are affected. This disease may account for up to 1% of individuals with severe mental retardation. Infants with cri du chat syndrome commonly have a distinctive cat-like cry. They also have an extensive grouping of abnormalities, with severe mental retardation being the most important.

23. Sex chromosomes abnormalities
Human development more tolerant of wrong numbers in sex chromosome
But produces a variety of distinct syndromes in humans
XXY = Klinefelter’s syndrome male
XXX = Trisomy X female
XYY = Jacob’s syndrome male
XO = Turner syndrome female

24. Klinefelter’s syndrome
XXY male
one in every 2000 live births
have male sex organs, but are sterile
feminine characteristics
some breast development
lack of facial hair
tall
normal intelligence

25. Klinefelter’s syndrome
How many Barr bodies would you expect?

26. Jacob’s syndrome male XYY Males 1 in 1000 live male births
extra Y chromosome
slightly taller than average
more active
normal intelligence, slight learning disabilities
delayed emotional maturity
normal sexual development

27. Trisomy X XXX 1 in every 2000 live births produces healthy females
Why?
Barr bodies
all but one X chromosome is inactivated
How many Barr bodies would you expect?

28. Turner syndrome Monosomy X or X0 1 in every 5000 births
varied degree of effects
webbed neck
short stature
sterile
How many Barr bodies would you expect?
??How many Barr bodies??

29. Changes in chromosome structure
deletion
loss of a chromosomal segment
duplication
repeat a segment
inversion
reverses a segment
translocation
move segment from one chromosome to another
error of replication
error of crossing over

30. Cri du Chat Deletion in chromosome 5
Infant’s cry sounds like high pitched cat meow