1. The Chromosomal Theory of Inheritance
Chapter 15

5. It’s important that you can relate the idea of genes on chromosomes to how we work and decipher genetics problems and how they relate to meiosis.

14. Sex Chromosomes and Inheritance
Morgan – discovered sex chromosomes and sex-linked genes; used fruit flies
XY – male – heterogametic; Y contains a gene “Sry” – sex determining region which triggers testicular development
X and Y have no homologous loci.
Y encodes traits only found in males; contains very few genes

15. Evidence for the chromosomal theory of inheritance
Walter Sutton – parallels between chromosomes and Mendel’s factors
Thomas Morgan – Mendel’s factors are on the chromosomes

17. Y encodes traits only found in males; contains very few genes
Y encodes traits only found in males; contains very few genes. Genes on the Y chromosome- holandric genes
Hairy ears in men

19. XX – females – homogametic
X inactivation in females
In embryonic cells inactivate one of the X’s and it contracts to form a dense body called a Barr body which is inactive except in gonadal cells undergoing meiosis
Barr bodies are highly methylated (-CH3 attached to the DNA)

20. Barr Bodies

21. Sex traits can be categorized into three types of inheritance:
sex-limited,
sex-linked, and
sex-influenced.

22. Sex-Limited Traits
Sex-limited traits are generally autosomal traits that are visible only within one sex.
There are genes which influence how much milk a lactating mother produces when she’s nursing a baby. These genes are carried by both males and females, but only females ever express them.

23. Sex-Linked Traits
Sex-linked traits would be considered traits like sickle cell anemia and color blindness. They are said to be linked because more males (XY) develop these traits than females (XX). This is because the females have a second X gene to counteract the recessive trait. Thus, the trait is more likely to be visible in the male.

24. Another interesting observation about X-linked traits is that males always receive their X chromosomes from their mothers, so they also receive any X-linked traits from their mother.

25. In pedigrees, sex-linked traits appear more in males.

26. Sex-Influenced Traits
Sex-influenced traits are autosomal traits that are influenced by sex. What makes these traits unusual is the way they are expressed phenotypically. In this case, the difference is in the ways the two genders express the genes.  
If a male has one recessive allele, he will show that trait, but it will take two recessive for the female to show that same trait.

27. One such gene is baldness.
This gene has two alleles, “bald” and “non-bald.” The behaviors of the products of these genes are highly influenced by the hormones in the individual, particularly by the hormone testosterone.
All humans have testosterone, but males have much higher levels of this hormone than females do.

28. The result is that in males, the baldness allele behaves like a dominant allele, while in females it behaves like a recessive allele.
As in all cases, dominance only matters in the heterozygote, so this means that heterozygous males will experience hair loss and heterozygous females will not. Even homozygous females may experience no more than a thinning of their hair, but many develop bald spots or have receding hairlines.

29. Baldness bb
Bb or bb

30. Problem: Will a bald female with a normal nonbald husband have bald kids?
bb wife x BB husband
All kids will be Bb, therefore girls will
be normal (nonbald) but their boys
will eventually be bald.

31. How to do sex-linked crosses
Sex chromosomes have to be indicated and sex of offspring has to be given
Two ways:
XAXA x XaY- nothing on the Y! OR
AA x aY

32. Xr Xr x XRY XrXR all females red XrY all males white
Ex: Red (R)/white (r) eye color is inherited as a sex-linked trait in fruit flies. What could you expect from a cross of a white-eyed female with a red-eyed male?
Xr Xr x XRY
XrXR all females red
XrY all males white

33. Sex-linked traits in humans
Color-blindness
Hemophilia
Duchenne muscular dystrophy

34. Are you colorblind?

36. Did you know?
Color Blindness, medically known as Daltonism or deuteranopia is a common malady, especially among men.
There are an estimated 10 million colorblind people driving cars in the US and they often can't see the difference between a red and a green light.

37. A person with hemophilia and a bruise.

38. Muscular Dystrophy

39. Many human traits follow Mendelian patterns of inheritance
Humans are not good subjects for genetic research
– Generation time is too long
– Parents produce relatively few offspring
– Breeding experiments are unacceptable
However, basic Mendelian genetics endures as the foundation of human genetics
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40. Pedigree Analysis
A pedigree is a family tree that describes the interrelationships of parents and children across generations
Inheritance patterns of particular traits can be traced and described using pedigrees
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

41. Pedigree / Family Tree Analysis
Shaded symbols indicate that the individual is affected, NOT if the trait is dominant or recessive… you have to figure that out!
Autosomes = chromosomes 1-22

42. Pedigrees can also be used to make predictions about future offspring
If trait is sex-linked, it will appear more in males.
If trait is recessive, it may appear in the offspring without being in the parents, skips generations
It trait is dominant, it will appear generally in most generations. For an offspring to have it, one of the parents should have it.

43. Key Male Affected male Mating Offspring, in birth order
Fig a
Key
Male
Affected
male
Mating
Offspring, in
birth order
(first-born on left)
Female
Affected
female
Figure Pedigree analysis

44. (a) Is a widow’s peak a dominant or recessive trait?
Fig b
1st generation
(grandparents) Ww ww ww Ww
2nd generation
(parents, aunts,
and uncles) Ww ww ww Ww Ww ww
3rd generation
(two sisters) WW ww or
Figure 14.15a Pedigree analysis Ww
Widow’s peak
No widow’s peak
(a) Is a widow’s peak a dominant or recessive trait?

45. (b) Is an attached earlobe a dominant or recessive trait?
Fig c
1st generation
(grandparents) Ff Ff ff Ff
2nd generation
(parents, aunts,
and uncles) FF or Ff ff ff Ff Ff ff
3rd generation
(two sisters) ff FF or Ff
Figure 14.15b Pedigree analysis
Attached earlobe
Free earlobe
(b) Is an attached earlobe a dominant or recessive trait?

46. ___________
_________

47. How is this trait inherited?

48. What is the manner of inheritance of this trait?
Fig. 14-UN5
What is the manner of inheritance of this trait?
George
Arlene
Sandra
Tom
Sam
Wilma
Ann
Michael
Carla
Daniel
Alan
Tina
Christopher

49. Inheritance of hemophilia in the royal families of Europe
What is the manner of inheritance of this trait?

50. Problems

51. Linked Genes Genes located on the same chromosomes
Tend to be inherited together
Do not follow predicted ratios of independently assorting chromosomes, i.e. 9:3:3:1 for AaBb x AaBb or 1:1:1:1 for AaBb x aabb (test cross).

52. Got 83% gray, normal and black, vestigial flies (Parent types)
Ex. Morgan crossed a wild type (gray body, normal wing) fly with a mutant recessive black body/vestigial wing fly.
TtNn x ttnn
Expected 1:1:1:1
Got 83% gray, normal and black, vestigial flies (Parent types)
17% recombinant types – black, normal and gray, vestigial

53. These are
recombinants from cross-overs.
17%
These are
parent-types.
83%

54. The high % of parent types indicated LINKED genes
The small number of recombinant types indicated CROSSING-OVER.
The % of recombinant offspring is called RECOMBINATION FREQUENCY.
We did this with the
Neurospora fungi.

55. How to figure out distance between genes
How to figure out distance between genes? Need to determine recombination frequency
To figure out the recombination frequency, divide the number of recombinants by the total number of counted organisms.

56. In the previous example: total flies: 2300
Number of recombinants = 391
% recombinants = 391/2300 = .17 or 17%

57. 1% recombinant frequency due to cross-over = 1 map unit
So 17% recombinants = 17 map units between genes for body color and wing types

58. Making Genetic Maps – an ordered list of genes on a chromosome

59. A.H. Sturdevant suggested that
Recombination frequencies reflect the relative distance between genes
Genes located farther apart have a greater probability of crossover
In a linkage map, one map unit (centimorgan) = to 1% crossover
We can use recombination data to figure out the order.

60. Create a linkage map for the following:
J,k 12% j,m 9% k,l 6% l,m 15%

61. ----------------15------------------
M j l k

62. Ex: Two types of flies, one WwLl (long wing, long leg) are test crossed with wwll (dumpy wing, short leg). Results: 20 long wings, long legs dumpy wings, short legs long wing, short legs dumpy wing, long legs (a) Are the gene linked? (b) What is the distance between the two genes (W,L)?
YES! The results do not reflect the 1:1:1:1 that you expected if the genes were not linked. Instead there were a lot of parent types.
To find the distance, add up the recombinants (3+4=7) and divide by the total number of flies counted (51). The answer is 13.7% so the number of map units between the genes is 13.7.

63. Linkage maps provide a sequence but not the exact location of the genes.
Cytogenetic maps locate gene loci by banded patterns on the chromosome.

64. However…. Frequency of recombinant gemetes
approaches but cannot exceed 50%.
50% recombinant gametes = 1:1:1:1
(2 parental : 2 recombinant) -- This
would be indistinguishable from 2
non-linked, independently assorting

65. Why did Mendel miss linkage?
Mendel could not note linkage because of the seven characters be studied in garden pea, most of them are located in different (non-homologous) chromosomes.
Seed color and flower color are in the same chromosome i.e, they are linked. However, they lie so far apart that they get separated by crossing over, and assort independently in all cases.

66. Impact of Environment on Genetic Expression (“Nature vs. Nurture”)
Norm of reaction = range of phenotypic variability under environmental conditions
Limited norm of reaction:
IA IA is always A blood type
Wide norm of reaction:
in neutral or basic soil, hydrangea flowers are pink; in acidic soil, they are violet to blue
More UV exposure  increased melanin production, darker skin pigmentation
Multifactorial disorders like cancer and diabetes have environmental & genetic components.

67. Wide norm of reaction (continued)
Himalayan rabbits carry the C gene, which is required for the development of pigments in the fur, skin, and eyes.
The C gene is inactive above 35°C, and it is maximally active from 15°C to 25°C.
Temperature regulation of gene expression produces rabbits with a distinctive coat coloring:
In warm, central parts of the body, the gene is inactive, and no pigments are produced, causing the fur color to be white
In the rabbit's extremities (ex: ears, tip of the nose, and feet), where the temperature is lower than 35°C, the C gene actively produces pigment, making these parts of the animal black.

68. Chromosome Abnormalities can often be detected with karyotypes
A. Numbers:
Due to nondisjunction – failure of homologous chromosomes to separate during Meiosis I or chromatids in Meiosis II.

69. Nondisjunction

70. What is a karyotype? MALE The arrangement of
the homologous pairs of chromosomes in order from longest to shortest, ending with the sex
chromosomes.
MALE

71. Aneuploidy – abnormal chromosome number
Trisomic – triplicate chromosomes
(2n + 1)
- found in Down syndrome – trisomy 21
- Klinefelter’s XXY – sterile male
- Extra Y - XYY male (taller, lower
intelligence)
- Triple X – XXX female (normal, fertile)

72. Karyotype of Down Syndrome female

73. Klinefelter’s syndrome XXY male

74. Monosomic – missing a chromosome
Ex – Turner’s syndrome, XO female; only known viable human monosomy

75. Turner’s Syndrome

76. Polyploidy - more than 2 complete sets of chromosomes
Triplody (3n) abnormals 2n egg and sperm
Tetraploidy (4n) – 2n zygote undergoes mitosis w/o cytokinesis
Common in plants

77. B. Structural Abnormalities in chromosomes
Deletion – piece may be lost or joined to a homologous chromosome (duplication) or to a nonhomologous one (translocation) or reattached in reverse order (inversion)

82. Two nonhomologous chromosomes have gene orders, respectively, of
A-B-C-D-E-F-G-H-I-J and
M-N-O-P-Q-R-S-T.
What type of chromosome alteration occurred if the daughter cells had
A-B-C-O-P-Q-G-J-I-H ?

83. A specific deletion of a small portion of chromosome 5; these children have severe mental retardation, a small head with unusual facial features, and a cry that sounds like a distressed cat.

84. Cri-du-Chat Syndrome (deletion)

85. Fragile X Syndrome (duplication)

86. Fragile X: the most common form of mental retardation
Fragile X: the most common form of mental retardation. The X chromosome of some people is unusually fragile at one tip - seen "hanging by a thread" under a microscope. Most people have 29 "repeats" at this end of their X-chromosome, those with Fragile X have over 700 repeats due to duplications. Affects 1:1500 males, 1:2500 females.

87. Translocation
A fragment of a chromosome is moved from one chromosome to another - joins a non-homologous chromosome.
The balance of genes is still normal (nothing has been gained or lost) but can alter phenotype as it places genes in a new environment.
Acute Myelogenous Leukemia is caused by this translocation:

88. Did you know….
Out of 15,000 spontaneous abortions, 7,500 are due to chromosomal abnormalites.
Out of 85,000 live births, 550 have chromosomal abnormalities.
113 out of 500 births exhibit trisomy 21 (Down’s Syndrome)

89. Video: Ultrasound of Human Fetus I
Fetal Testing
In amniocentesis, the liquid that bathes the fetus is removed and tested
In chorionic villus sampling (CVS), a sample of the placenta is removed and tested
Other techniques, such as ultrasound and fetoscopy, allow fetal health to be assessed visually in utero
Video: Ultrasound of Human Fetus I
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

90. (b) Chorionic villus sampling (CVS)
Fig
Amniotic fluid
withdrawn
Centrifugation
Fetus
Fetus
Suction tube
inserted
through
cervix
Placenta
Placenta
Chorionic
villi
Uterus
Cervix
Fluid
Bio-
chemical
tests
Fetal
cells
Several
hours
Fetal
cells
Several
hours
Several
weeks
Figure Testing a fetus for genetic disorders
Several
weeks
Several
hours
Karyotyping
(a) Amniocentesis
(b) Chorionic villus sampling (CVS)

91. Phenotypic effects due to inheritance of maternal/paternal chromosomes
Genomic imprinting – genes are imprinted depending if they were inherited from the mom or dad
ex – chromosome 15 deletion from father – Prader-Willi syndrome
ex – from mom - Angelman syndrome

92. Prader-Willi Syndrome
Common cause of childhood obesity, poor muscle tone
Chromosome 15 deletion in father

93. Angelman Syndrome
AS is characterized by intellectual and developmental delay, speech impediment, sleep disturbance, unstable jerky gait, seizures, hand flapping movements, frequent laughter/smiling.
Chromosome 15 deletion in mother

94. Ex – Fragile X – triplet repeats (CGG) occurs about 200 times at tip of X chromosome – most likely to occur in maternal X.
Females with the disorder are more likely to have less impairment and less obvious physical characteristics.
ex – Huntington’s Disease – chrom 4 has CAG repeats, most common in father’s alleles.

95. Huntington’s Disease
Huntington’s disease is a degenerative disease of the nervous system
The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age
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96. Inheritance of extranuclear Genes
In plastids and mitochondria
Not inherited in Mendelian fashion
Inheritance of their DNA is maternal
May be implicated in diabetes, Alzheimer’s and heart disease

97. The Behavior of Recessive Alleles
Recessively inherited disorders show up only in individuals homozygous for the allele
Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal (i.e., pigmented)
Albinism is a recessive condition characterized by a lack of pigmentation in skin and hair

98. Parents Normal Normal Aa Sperm A a Eggs Aa AA A Normal (carrier)
Fig
Parents
Normal
Normal Aa  Aa
Sperm A a
Eggs Aa AA A
Normal
(carrier)
Normal
Figure Albinism: a recessive trait Aa aa a
Normal
(carrier)
Albino

99. If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low
Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele
Most societies and cultures have laws or taboos against marriages between close relatives
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100. Cystic Fibrosis
Cystic fibrosis is the most common lethal genetic disease in the United States,striking one out of every 2,500 people of European descent
The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes
Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

101. Sickle-Cell Disease
Sickle-cell disease affects one out of 400 African-Americans
The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells
Symptoms include
physical weakness,
pain, organ damage,
and even paralysis

102. Dominantly Inherited Disorders
Some human disorders are caused by dominant alleles
Dominant alleles that cause a lethal disease are rare and arise by mutation
Achondroplasia is a form of dwarfism caused by a rare dominant allele
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103. Parents Dwarf Normal Sperm Eggs Dwarf Normal Dwarf Normal Dd dd D d Dd
Fig
Parents
Dwarf
Normal Dd  dd
Sperm D d
Eggs Dd dd d
Figure Achondroplasia: a dominant trait
Dwarf
Normal Dd dd d
Dwarf
Normal

104. Multifactorial Disorders
Many diseases, such as heart disease and cancer, have both genetic and environmental components
Little is understood about the genetic contribution to most multifactorial diseases
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

105. Many polygenic traits are multifactorial…
Many polygenic traits are multifactorial….environment can influence their expression
Intelligence
Weight
Common diseases (heart disease, cancer)
Addiction
Behaviorial disorders

107. Know your family history!

108. Case Study: Blue People of Kentucky

109. Lorenzo “Blue Anze” and Eleanor Fugate 1915

111. Fruit Fly Lab

113. Life cycle

114. Examine the traits.
We have three mutants (white eyes, sepia eyes, vestigial wings), and the wild type fly (red eyes, normal wings).

115. Vestigial Wings

116. Describe their phenotypes in your lab notebook.
While you are examining the fly types, make sure you can distinguish the male flies from the female flies. Make notations in your lab notebook.

117. Sexes of Fruit Flies

121. Remember…
The crosses you will be examining are the F1 flies from pure-breeding parents.
Not the parents!

122. You will be given a F1 cross to count. Put them to sleep and count them. Make sure you count male and female flies separately. Put counts in your lab notebook.
We will share this data among the class.
You will then take 7 pairs of the F1 flies to make a new cross (the F2) in a bottle. Make sure you label your bottle with your period, the cross number, and name of someone in your group.
ex- 1 #2 John

123. You will remove the F2 parents in about two weeks and then start to look for the offspring. When the offspring hatch, you will start counting for about 10 days. Everyone in your group counts.
After you count, put the flies in the morgue.

124. Crosses Wild (red-eyed) males x sepia-eyed females
Wild (red-eyed) males x white-eyed females
Sepia-eyed, normal wing males x red-eyed, vestigial wing females (2 trait cross)