1. Ch. 15 Warm-Up Definitions: Sex-linked gene Barr body SRY gene
Linked genes
Linkage map
Ch. 15 Warm-Up
A white-eyed female fruit-fly is mated with a red-eyed male. What genotypes and phenotypes do you predict for the offspring?
Neither Tim nor Rhoda has Duchenne muscular dystrophy (X-linked recessive disorder), but their firstborn son has it. What is the probability their 2nd child will have it?
Colorblindness is a sex-linked recessive trait. A colorblind male and a female with normal vision have a son who is colorblind. What are the parents’ genotypes?

2. Warm up What is a Barr body?
How are linkage maps constructed? (See. Fig in Campbell 9th ed.)
Determine the sequence of genes along a chromosome based on the following recombination frequencies: A-B, 8 map units; A-C, 19 map units; A-D, 20 map units; B-C, 11 map units; B-D, 28 map units.
What does a frequency of recombination of 50% indicate?

3. Warm-Up
What is the pattern of inheritance of the trait (shaded square/circle) shown in the pedigree?
How many chromosomes are in a human cell that is:
a) Diploid? b) Triploid?
c) Monosomic? d) Trisomic?

4. THE CHROMOSOMAL BASIS OF INHERITANCE
CHAPTER 15

5. What you must know:
How the chromosome theory of inheritance connects the physical movement of chromosomes in meiosis to Mendel’s laws of inheritance.
The unique pattern of inheritance in sex-linked genes.
How alteration of chromosome number or structurally altered chromosomes (deletions, duplications, etc.) can cause genetic disorders.
How genetic imprinting and inheritance of mitochondrial DNA are exceptions to standard Mendelian inheritance.

6. Chromosome theory of inheritance:
Genes have specific locations (loci) on chromosomes
Chromosomes segregate and assort independently
Chromosomes tagged to reveal a specific gene (yellow).

7. Thomas Hunt Morgan Drosophila melanogaster – fruit fly
Fast breeding, 4 prs. chromosomes (XX/XY)
Sex-linked gene: located on X or Y chromosome
Red-eyes = wild-type; white-eyes = mutant
Specific gene carried on specific chromosome

8. Sex determination varies between animals

9. Sex-linked genes Sex-linked gene on X or Y Females (XX), male (XY)
Eggs = X, sperm = X or Y
Fathers pass X-linked genes to daughters, but not sons
Males express recessive trait on the single X (hemizygous)
Females can be affected or carrier

10. Transmission of sex-linked recessive traits

11. Sex-linked disorders Colorblindness Duchenne muscular dystrophy
Hemophilia

13. X-Inactivation
Barr body = inactive X chromosome; regulate gene dosage in females during embryonic development
Cats: allele for fur color is on X
Only female cats can be tortoiseshell or calico.

14. Human development Y chromosome required for development of testes
Embryo gonads indifferent at 2 months
SRY gene: sex-determining region of Y
Codes for protein that regulates other genes

15. Genetic Recombination: production of offspring with new combo of genes from parents
If offspring look like parents  parental types
If different from parents  recombinants

16. If results do not follow Mendel’s Law of Independent Assortment, then the genes are probably linked

17. Linked genes: located on same chromosome and tend to be inherited together during cell division

18. Gene Linkage Genes found on same chromosome are considered LINKED!
How close or far away are they?
Fewer gamete possibilities the closer they are!
Why? Less possibility for crossing over to occur.
Independent assortment does not apply
No linkage if genes are on separate chromosomes (# of recombinants increases)

20. Calculating recombination frequency

21. This shows linked genes with no crossing over and crossing over.
How can we test to see if genes are linked?

22. Mendelian Testcross no linkage
Phenotypic ratio: 1 : 1 : 1 : 1
Frequency: 25% : 25%: 25% : 25%

23. Crossing over: explains why some linked genes get separated during meiosis
the further apart 2 genes on same chromosome, the higher the probability of crossing over and the higher the recombination frequency

24. Linkage Map: genetic map that is based on % of cross-over events
1 map unit = 1% recombination frequency
Express relative distances along chromosome
50% recombination = far apart on same chromosome or on 2 different chromosomes

25. Chromosome Mapping Calculate the frequency of recombinant offspring.
Recombination frequency = # map units
Ex: 13% recombinant frequency = 13 map units
Greater % = greater distance
Lower % = closer distance

28. Exceptions to Mendelian Inheritance

29. Genomic Imprinting
Genomic imprinting: phenotypic effect of gene depends on whether from M or F parent
Methylation: silence genes by adding methyl groups to DNA

30. Non-Nuclear DNA Some genes located in organelles
Mitochondria, chloroplasts, plastids
Contain small circular DNA
Mitochondria = maternal inheritance (eggs)
Variegated (striped or spotted) leaves result from mutations in pigment genes in plastids, which generally are inherited from the maternal parent.

31. Genetic Testing Reasons for Genetic Tests:
Diagnostic testing (genetic disorders)
Presymptomatic & predictive testing
Carrier testing (before having children)
Pharmacogenetics (medication & dosage)
Prenatal testing
Newborn screening
Preimplantation testing (embryos)

32. Prenatal Testing May be used on a fetus to detect genetic disorders
Amniocentesis: remove amniotic fluid around fetus to culture for karyotype
Chorionic villus sampling: insert narrow tube in cervix to extract sample of placenta with fetal cells for karyotype

34. Human Chromosome Disorders
Some have high frequency in humans
most embryos are spontaneously aborted
developmental problems result from biochemical imbalance
Certain conditions are tolerated
upsets the balance less = survivable
characteristic set of symptoms = syndrome

35. Chromosomal Abnormalities
Nondisjunction
chromosomes don’t separate properly during meiosis
Chromosomal Mutations
deletion
duplication
inversion
translocation

36. Nondisjunction: chromosomes fail to separate properly in Meiosis I or Meiosis II

37. 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

38. Karyotyping can detect nondisjunctions.
Down Syndrome = Trisomy 21

39. Klinefelter Syndrome: 47XYY, 47XXY
Nondisjunction
Klinefelter Syndrome: 47XYY, 47XXY

40. Autosomal Disorders Dominant Recessive Acondroplasia Acromegaly
Dwarfism
Lethal in homozygous cond.
Acromegaly
Gigantism
Overactive pituitary
Huntington’s
Degeneration of nervous system
Manifests around 40 years of age
Recessive
Albinism
Melanin pathway mutated
photosensitivity
Phenylketoneuria
Cannot break down phenylalanine
Lead to mental retardation
Cystic fibrosis
Cl- channel problem
Mucus buildup
Death around 40

41. 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 - aneuploidy 2n
n-1 n
n+1

42. Nondisjunction
Turner Syndrome = 45XO

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

44. Nondisjunction Aneuploidy: incorrect # chromosomes
Monosomy (1 copy) or Trisomy (3 copies)
Polyploidy: 2+ complete sets of chromosomes; 3n or 4n
Rare in animals, frequent in plants
A tetraploid mammal. Scientists think this species may have arisen when an ancestor doubled its chromosome # by errors in mitosis or meiosis.

45. 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.

46. Down syndrome & age of mother
Mother’s age
Incidence of Down Syndrome
Under 30
<1 in 1000 30
1 in 900 35
1 in 400 36
1 in 300 37
1 in 230 38
1 in 180 39
1 in 135 40
1 in 105 42
1 in 60 44
1 in 35 46
1 in 20 48
1 in 16 49
1 in 12
Rate of miscarriage due to amniocentesis:
1970s data 0.5%, or 1 in 200 pregnancies
2006 data <0.1%, or 1 in 1600 pregnancies

47. Sex Chromosomes Abnormalities
Human development more tolerant of wrong numbers in sex chromosome
Cause is nondisjunction
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

48. Review Questions
What is the pattern of inheritance of the trait (shaded square/circle) shown in the pedigree?
How many chromosomes are in a human cell that is:
a) Diploid? b) Triploid?
c) Monosomic? d) Trisomic?

49. Chi-Square Analysis Practice
Two true-breeding Drosophila are crossed: a normal-winged, red-eyed female and a miniature-winged, vermillion-eyed male. The F1 offspring all have normal wings and red eyes. When the F1 offspring are crossed with miniature-winged, vermillion-eyed flies, the following offspring resulted:
233 normal wing, red eye
247 miniature wing, vermillion eye
7 normal wing, vermillion eye
13 miniature wing, red eye
What type of conclusions can you draw from this experiment? Explain your answer.