1. CHAPTER 14
THE HUMAN GENOME

2. 14-1 Human Heredity

3. Key Concepts
How is sex determined?
How do small changes in DNA cause genetic disorders?

4. How do biologists go about studying human DNA?
They use something called a KARYOTYPE
Biologists photograph cells in mitosis, when chromosomes are easier to see. They cut out the chromosomes from the photographs and group them together in pairs

5. Humans have a total of 46 chromosomes – half (23) from mom and half (23) from dad
Out of those 46, two are called SEX CHROMOSOMES
Determine an individual’s sex
Females have two copies of
a larger X chromosome
Males have one large X
and a smaller Y chromosome

6. AUTOSOMES
The other 44 chromosomes
Females – 46XX
Males - 46XY

7. How is the X chromosome different from the Y chromosome?
Look at the karyotype in your notes, is this individual male or female?
Male
How is the X chromosome different from the Y chromosome?
The X chromosome is longer

8. All egg cells carry a single X chromosome.
How is sex determined?
All egg cells carry a single X chromosome.
However, half of all sperm cells carry an X chromosome.
This ensures that about half of the zygotes will be 46XX and half will be 46XY

9. Finish this Punnett Square to see how sex is determinedY

10. X XX Y XY

11. How do biologists identify an inherited trait that is controlled by a single gene?
They must establish that the trait is actually inherited and not a result of environmental influences
-They have to study how the trait is passed from one generation to the next

12. Shows the relationship within a family; helps to study genetic traits
PEDIGREE
Shows the relationship within a family; helps to study genetic traits
Can help parents understand the probability of having a child with a genetic disorder

13. Figure 14-3 A Pedigree Go to Section: A circle represents a female.
A square represents a male.
A horizontal line connecting a male and female represents a marriage.
A vertical line and a bracket connect the parents to their children.
A half-shaded circle or square indicates that a person is a carrier of the trait.
A circle or square that is not shaded indicates that a person neither expresses the trait nor is a carrier of the trait.
A completely shaded circle or square indicates that a person expresses the trait.
Go to Section:

14. What do circles represent?
-Females
What do squares represent?
-Males
What does a horizontal line represent?
Between a male and female represents a marriage
What does a vertical line represent?
Connects parent to their children

15. What does a circle or square that is not shaded represent?
-That person does not express a trait nor are they a carrier
What does a fully shaded circle or square represent?
-The person expresses a trait

16. What does a half shaded circle or square represent?
The person is a carrier of the trait
What is the sex of the last person in the second row? Does that person have the trait?
Female; no

17. Pedigree analysis reveals Mendelian patterns in human inheritance
data mapped on a family tree
= male
= female
= male w/ trait
= female w/ trait

18. POLYGENIC
A trait controlled by many genes
How can you find out where you get your good looks from?
This is actually rather difficult
Many traits are polygenic like the shape of your eyes or ears
Many of your traits are only partly governed by genetics – environmental influences (nutrition, exercise) can affect how a trait is expressed

19. What is your blood type?
Why is it important for a doctor to know your blood type before they give you a blood transfusion?
Using the wrong blood type during a transfusion can be fatal

20. The best known blood groups are ABO and Rh
-Rh blood group is determined by a single gene with two alleles –
positive and negative
-Rh stands for rhesus monkey – this was the first animal where they discovered this factor

21. The positive allele is dominant
–If you are Rh+/Rh+ or Rh+/Rh- you are considered Rh positive
The negative allele is recessive
If you have two Rh- alleles you are
Rh negative

22. ABO a little more complicated There are three alleles IA, IB, and I
Alleles IA and IB are codominant
These alleles produce molecules known as antigens that your immune system can recognize on the surface of red blood cells
If you have IAIA you only produce A antigens etc. – see fig 14-4 p. 344

23. Figure 14-4 Blood Groups Go to Section: Safe Transfusions Phenotype
(Blood Type
Antigen on
Red Blood Cell
Genotype To
From
Go to Section:

24. If you are homozygous ii you have no antigen on your red blood cells this is blood type O
Typically nurses and doctors will use both blood types like AB negative or O positive

25. What happens if you give type A blood to a type O patient?
The immune system will recognize the blood cells as foreign (they don’t belong) because of the A antigens on the cell’s surfaces. The immune system will produce antibodies against these blood cells and destroy them

26. Why are type AB people called universal acceptors?
They can accept any blood type
Why are type O called universal donors?
They can donate to any blood type
What blood type do you think most blood banks want to have on hand?
Type O because is has no antigens and can be given to any blood type without causing an antibody reaction

27. If a woman with type O blood and a man with type AB blood have children, what are the children’s possible phenotypes?
Use a Punnett Square to answer

28. IA IB i

29. Genotypes: IAi and IBi Phenotypes: Type A and Type B

30. Genetic Disorders-they are disorders that are inherited in our genes
Autosomol
Disorders
caused by
Recessive alleles
Dominant alleles
Codominant alleles
include
include
include
Albinism
Galactosemia
Tay-Sachs disease
Huntington’s disease
Sickle cell disease
Cystic fibrosis
Phenylketonuria
Achondroplasia
Hypercholes-
terolemia
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31. If there is a known genetic condition a doctor may suggest a couple go through genetic counseling to determine their risk of having a child with an inherited genetic condition.
A pedigree can help us understand the past & predict the future
Thousands of genetic disorders are inherited as simple recessive traits
benign conditions to deadly diseases
albinism
cystic fibrosis
Tay sachs
sickle cell anemia
PKU

32. Genetic testing - may be done to determine if an unborn child has a genetic disorder. Example: Amniocentesis

33. Recessive diseases
The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all
Heterozygotes (Aa)
carriers
have a normal phenotype because one “normal” allele produces enough of the required protein

34. Aa A a A a AA Aa A a AA Aa Aa A a Aa aa Aa aa
Heterozygote crosses
Heterozygotes as carriers of recessive alleles
Aa x Aa Aa A a A a
male / sperm AA Aa A a
female / eggs AA Aa Aa A a Aa aa Aa aa

35. Albinism – homozygous recessive (aa)

36. Phenylketonuria – PKU
People lack an enzyme to break down phenylalanine
Phenylalanine is an amino acid found in milk and many other foods
If a child with PKU eats phenylalanine and it builds up in their tissues – mental retardation occurs
There is a test
Treatment – the person must be on a low-phenylalanine diet their entire life
Caused by a recessive allele on chromosome 12

37. Tay-Sachs strikes 1 in 3600 births
Primarily Jews of eastern European (Ashkenazi) descent & Cajuns
strikes 1 in 3600 births
100 times greater than incidence among non-Jews or Mediterranean (Sephardic) Jews
non-functional enzyme fails to breakdown lipids in brain cells
symptoms begin few months after birth
seizures, blindness & degeneration of motor & mental performance
child dies before 5yo

38. Tay-Sachs disease (continued)
Caused by an allele found in Jewish families with central and eastern European ancestry
Results in nervous system breakdown and death in the first few years of life
There is no treatment
Parents can be tested ahead of time to see if they are carriers

39. Dominant allele disorders
Achondroplasia
One type of dwarfism
The person never reaches a height greater than 4 feet 4 inches tall
Arms and legs form disproportionately short
1 in about 10,000 people are affected

40. Huntington’s disease
Causes progressive loss of muscle control and mental function until death occurs
Symptoms don’t show until people are in their thirties and forties

41. Codominant allele disorders
Sickle cell anemia
Primarily Africans
strikes 1 out of 400 African Americans
caused by substitution of a single amino acid in hemoglobin
when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods
Due to this shape the cells are more rigid and they tend to get stuck in capillaries causing blockages
Causes physical weakness, brain damage, damage to the heart and spleen
deforms red blood cells into sickle shape
sickling creates pleiotropic effects = cascade of other symptoms

42. Doctors can use regular blood transfusions to prevent brain damage and new drugs to prevent or treat other problems.

43. 2 alleles are codominant
Sickle cell phenotype
2 alleles are codominant
both normal & abnormal hemoglobins are synthesized in heterozygote (Aa)
carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stress
exercise

44. Heterozygous people still have sickle shaped red blood cells but not as many
When the body destroys sickled cells, it gets rid of the Malaria parasite at the same time
In regions where Malaria is a problem, it is beneficial for people to be heterozygous for sickle cell disease

45. Heterozygote advantage
Malaria
single-celled eukaryote parasite spends part of its life cycle in red blood cells
Heterozygous people still have sickle shaped red blood cells but not as many
When the body destroys sickled cells, it gets rid of the Malaria parasite at the same time
In regions where Malaria is a problem, it is beneficial for people to be heterozygous for sickle cell disease
In tropical Africa, where malaria is common:
homozygous normal individuals die of malaria
homozygous recessive individuals die of sickle cell anemia
heterozygote carriers are relatively free of both

46. Malaria, a serious parasitic disease that infects red blood cells, is common in certain regions of Africa. People who are heterozygous for sickle cell disease are generally healthy and they are resistant to Malaria

47. Prevalence of Malaria
High frequency of sickle cell allele in African Americans is vestige of African roots
Prevalence of Sickle Cell Anemia

48. Cystic Fibrosis
Common in people whose ancestors come from Northern Europe
strikes 1 in 2500 births
1 in 25 whites is a carrier (Aa)
Recessive allele on chromosome number 7 the normal allele codes for a membrane protein that transports Cl- across cell membrane
defective or absent protein channels cause high extracellular levels of Cl-
thicker & stickier mucus coats around cells
mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections
Children with CF have serious digestive problems
They produce thick, heavy mucous that clogs their lungs and breathing passages
Without treatment children die before 5; with treatment can live past their late 20s

49. mucus secreting glands
Normal Lungs
Chloride channel
Transports chloride through protein channel out of cell.
Osmotic effects: H2O follows Cl-
Cl-
airway
Na+
cells lining lungs
In people without cystic fibrosis, working cystic fibrosis proteins allow salt (chloride) to enter the air space and water follows by osmosis. The mucus layer is dilute and not very sticky.
mucus secreting glands

50. bacteria & mucus build up thickened mucus hard to secrete
Cystic fibrosis
damaged lung tissue
Cl-
airway
Na+
bacteria & mucus build up
cells lining lungs
In people with cystic fibrosis, non-working cystic fibrosis proteins mean no salt (chloride) enters the air space and water doesn't either. The mucus layer is concentrated and very sticky.
People with cystic fibrosis have lung problems because:
Proteins for diffusion of salt into the airways don't work. (less diffusion)
Less salt in the airways means less water in the airways. (less osmosis)
Less water in the airways means mucus layer is very sticky (viscous).
Sticky mucus cannot be easily moved to clear particles from the lungs.
Sticky mucus traps bacteria and causes more lung infections.
Therefore, because of less diffusion of salt and less osmosis of water, people with cystic fibrosis have too much sticky mucus in the airways of their lungs and get lots of lung infections. Thus, they are sick a lot.
thickened mucus hard to secrete

52. Heterozygous Advantage
Heterozygous people are unaffected because they produce enough of this protein to allow their tissues to function properly

53. 14-2 Human Chromosomes

54. Key Concepts
Why are sex linked disorders more common in males, than in females?
What is nondisjunction, and what problems does it cause?

55. Look at page 341. Which chromosomes are the largest? 1 and 2
Which chromosomes are the smallest?
18-22
Considering the chromosome sizes, how many bases might chromosome 1 have if chromosome 22 has about 43 million bases?
About three times as many – 129 million

56. Chromosome 21 and 22 are the smallest human autosomes
These were the first two chromosomes whose sequences were discovered
Chromosome 22 has 545 genes
Problems with this chromosome
genetic disorders are: an allele associated with a form of leukemia and another associated with neurofibromatosis (a tumor-causing disease of the nervous system)

57. Chromosome 21 has 225 genes
Genetic disorders are: amyotrophic lateral sclerosis (ALS) also known as Lou Gehrigs disease
this disease causes a progressive loss of muscle control due to the destruction of nerves in the brain and spinal cord

58. Recall:
Genes located on the same chromosome are linked, meaning they tend to be inherited together
Genes may be separated by recombination (during crossing-over) in meiosis

59. Look at p. 350 fig 14-12
Which chromosome carries more genes?
The X chromosome
SEX-LINKED GENES
A gene located on the X or Y chromosome

60. More than 100 sex-linked genetic disorders have been mapped to the X chromosome
The Y chromosome is much smaller and appears to only carry a few genes

61. Why are sex-linked disorders more common in males than in females?
Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive.

62. Colorblindness the person cannot see certain colors
the human genes associated with colorblindness are located on the X chromosome
in males, a defective version of any one of these genes produces colorblindness
red-green colorblindness (cannot see green) found in 1 out of 10 males in US but only 1 in 100 females

63. Can you see the numbers in each circle?

64. Why do fewer females have colorblindness?
In order for a recessive allele, such as the one for colorblindness, to be expressed in females, there must be two copies of the allele

65. Pedigrees and pedigree Punnett squares are used to trace genetic disorders through families and to determine the chances that future generations will have the disorder

66. Figure 14-13 Colorblindness
Father
(normal vision)
Normal vision
Colorblind
Male
Female
Daughter
(normal vision)
Son
(normal vision)
Mother (carrier)
Daughter
(carrier)
Son
(colorblind)
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67. She is heterozygous and is a carrier
Why is the circle for the mother shaded only halfway?
She is heterozygous and is a carrier
Would you expect the colorblind son to have sons who are colorblind?
No, the son can only pass the Y chromosome to his sons
What is the probability that the daughter who is a carrier will have a colorblind child if she marries a man with normal vision?
25%

68. Hemophilia A protein necessary for normal blood clotting is missing
Two important genes carried on the X chromosome help control blood clotting – a recessive allele in either of these two genes may produce the disorder
1 in 10,000 males are born with it
People with hemophilia can bleed to death from a minor cut or could suffer internal bleeding from bumps or bruises
These people are treated with injections of clotting proteins

69. Duchenne Muscular Dystrophy
Results in the progressive weakening and loss of skeletal muscle
People rarely live past adulthood
1 in 3000 males is born with it

70. Calico cats Females have two X chromosomes, but males only have one
If just one X chromosome is enough for cells in males, how does the cell adjust to the extra X chromosome in female cells?
Scientists have found that in female cells, one X chromosome is randomly switched off

71. A gene that controls coat color is located on the X chromosome
One X chromosome may have an allele for orange spots and the other may have an allele for black spots.
In some cells on the cat’s body one X chromosome (orange spots) is switched on while the other X chromosome in those cells is switched off

72. Then in other areas the opposite occurs – the black spots X chromosome switches on and the other switches off
Male cats have only one X chromosome so they can only have spots of one color

73. The turned off chromosome forms a dense region in the nucleus known as a Barr Body
Barr bodies are not found in males because their X is always turned on
What is the sex of the cat in fig ?
Female

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

75. Nondisjunction
Problems with meiotic spindle cause errors in daughter cells
tetrad 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+1 n

76. Alteration of chromosome number

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

78. Human chromosome disorders
High frequency in humans
most embryos are spontaneously aborted
alterations are too disastrous
developmental problems result from biochemical imbalance
Certain conditions are tolerated
upset the balance less = survive
characteristic set of symptoms = syndrome

79. 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

80. Trisomy 21

81. 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

82. Genetic testing Amniocentesis in 2nd trimester sample of embryo cells
stain & photograph chromosomes
Analysis of karyotype

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

84. Klinefelter’s syndrome
XXY male
one in every 2000 live births
have male sex organs, but are sterile
feminine characteristics
tall
normal intelligence

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

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

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

88. XYY Males
How many Barr bodies would you expect?

89. Trisomy X XXX 1 in every 2000 live births produces healthy females
Why?
How many Barr bodies would you expect?

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

91. Turner syndrome

92. 14-3 Human Molecular Genetics

93. Key Concepts
What is the goal of the human genome project?
What is gene therapy?

94. Bioethics and You
As you become more aware of scientific advances in genetics, you might realize that with the ability to manipulate genes, there comes responsibility.
This ability provides an opportunity to improve the lives of many people.
But there is also a potential for errors or intentional misuse of the technology.
Go to Section:

95. If two prospective parents suspect they might be carrying recessive alleles for a genetic disorder such as cystic fibrosis or Tay-Sachs disease, how could they find out for sure?
Genetic tests have been developed that can spot abnormalities in DNA. Scientists can compare normal sequences with these parents’ DNA to see if they are carriers

96. DNA FINGERPRINTING
Analyzes sections of DNA that have little or no known function but vary widely from one person to the next – this tool can identify individuals

97. How to do DNA Fingerprinting
A sample of DNA with genes and repeats (“junk DNA”) is taken
Restriction enzymes cut the DNA into fragments containing genes and repeats
The DNA fragments are separated according to size using gel electrophoresis
Radioactive “probes” showing where the repeats are – this produces a series of bands
This has been used since the 1980’s
It not only helps to convict criminals but has also freed those who were wrongly accused

98. Our complete set of genetic information
HUMAN GENOME
Our complete set of genetic information

99. What is the Human Genome Project?
1990 the US and other countries began trying to sequence all human DNA
This project was completed in 2003
They have mapped 20,000 – 50,000 human genes
They know the sequence of 3 billion base pairs
Now that scientist know the entire human genome they are trying to figure out how to prevent certain genetic disorders

100. GENE THERAPY
The process of changing the gene that causes a genetic disorder – it is replaced by a normal working gene
Normal hemoglobin gene
Bone marrow cell
Chromosomes
Genetically engineered virus
Nucleus
Bone marrow
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101. Food for thought
Do you think it should be legal for people to affect their children’s characteristics?
What will happen to the human population if we gain the opportunity to design our bodies?

102. Key Concepts Answered:
How is sex determined?
All egg cells carry a single X chromosome (23X). However, half of all sperm cells carry an X chromosome (23X) and half carry a Y chromosome (23Y). This ensures that just about half of the zygotes will be 46XX and half will be 46XY. Egg cells contain a single X chromosome. Sperm cells contain either one X chromosome or one Y chromosome.
How do small changes in DNA cause genetic disorders?
a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder

103. Key Concepts Answered:
Why are sex linked disorders more common in males, than in females?
Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive.
What is nondisjunction, and what problems does it cause?
Nondisjunction causes gametes to have abnormal numbers of chromosomes. If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes, and a disorder of chromosome numbers may result.

104. Key Concepts Answered:
What is the goal of the human genome project?
 The Human Genome Project is an attempt to sequence all human DNA.
What is gene therapy?
In gene therapy, an absent or faulty gene is replaced by a normal, working gene.