1. Chapter 14
The Human Genome

2. Human Chromosomes Our Focus this Chapter: Karyotype Sex Determination
Genes and the Environment
Genes and Inheritance
Polygenic
Dominant vs. Recessive
Pedigree Charts and Punnett Squares
Human Genes
Inheritance Patterns
Gene Inheritance: Polygenic, dominant, recessive, codominant, sex-linked, linked
Chromosomal Disorders

3. Karyotype Autosomes: Body chromosomes (#1-22) Sex Chromosomes
Male or Female?
(hint: the one in your notes is different from this one)#23

4. Fertilization Chart
Haploid (23)
Diploid (46)

5. Sex Determination
Punnett Square
Probability:
50% male
50% female

6. Human Genes
What is a gene? A segment of DNA coding for a protein (phenotype)

7. Genes and the Environment
Influences on Gene Expression (phenotype)
Nature vs. Nurture
Gene expression
Nutrition
Exercise
Stress
epigenetics

8. Genes and Inheritance Polygenic Traits:
-Multiple genes on different chromosomes affecting one trait
Combination of dominant and recessive
Ex: Hair color, Eye Color, Height
Multiple Allele
More than 2 possible alleles, in the population,for 1 genes
Each individual still only has 2 alleles
Ex. Blood Type
IA, IB, i
UP to 8 genes that control eye color: From one source Right now there are three known gene pairs that control eye color. The bey 2 gene on chromosome 15 contains a brown and blue allele. Also on chromosome 15, the bey 1 gene is the central brown gene. On chromosome pair 19 the gey gene contains a green allele and a blue allele.
A green allele is dominant over a blue allele, and a brown allele is dominant over both green and blue alleles. For the bey 2 gene if a person has a brown allele then they will have brown eyes. In the gey gene the green allele is dominant over the blue allele, but it is still recessive next to a brown allele. For example if a person has a brown allele on chromosome 15, but all the other alleles are blue or green, they will have brown eyes. A green eyed person would have a green allele on chromosome 19 and all or some other blue alleles. Blue eyes are produced only with two blue eye genes. All four alleles must be blue to produce a blue eyed person.

9. Genes and Inheritance Dominant vs. Recessive Incomplete Dominance
Recessive alleles are masked
in the presence of a dominant allele
Incomplete Dominance
is a form of intermediate
inheritance in which one allele for a
specific trait is not completely
dominant over the other allele.
Codominant
-(blood type)

10. Pedigree Chart (traces family history)
Figure 14-3 A Pedigree
Section 14-1
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.
Use a Punnett Square (determines probability) to illustrate the genetic probability of the first couple’s offspring.
Problem Solving: p343

11. Blood Type Multiple Allele (A, B, O) Codominant (A and B)
Dominant/Recessive
(A & B are dominant over O)
. any of a type of specific antigen present on the surface of red blood cells, persons having inherited such antigens being designated Rh+ (Rh positive) and persons lacking them, a much smaller group, being designated Rh− (Rh negative) blood of Rh− persons is incompatible with Rh+ blood because of antibody reaction, and an Rh− woman who bears an Rh+ baby will have formed antibodies to the fetal blood that, unless removed from her bloodstream by apheresis in a subsequent pregnancy, will be carried across the placenta and destroy red blood cells of the next Rh+ fetus, resulting in erythroblastosis in the newborn.

13. Blood Type in the Human Population

14. Human Genes Blood Type Disorders Gene Chromosomal Autosomal Sex-linked
Recessive
Dominant
Codominant
Sex-linked
Chromosomal

15. Autosomal Recessive
Both copies of the gene must be the recessive allele
Represented by a lower case letter
Albinism –
Phenylketonuria –
Tay Sachs –
Galactosemia –
Cystic Fibrosis –
Chart p345

16. Autosomal Recessive Albinism Genotype: aa Expression:
Missing Melanin (pigment)
Lack of color in skin, hair and eyes
Vision impairment
Treatment:
Glasses, eye surgery

17. Autosomal Recessive Phenylketonuria (PKU) Genotype: (chromosome 12) pp
Expression:
Missing phenylalanine hydroxylase
Inability to process phenylalanine
Abnormal pigment
Mental retardation
Treatment
Specialized diet low in phenylalanine
Phenylalanine occurs in significant amounts in milk, eggs, and other common foods. The artificial sweetener NutraSweet (aspartame) also contains phenylalanine. Any products containing aspartame should be avoided.
A special infant formula called Lofenalac is made for infants with PKU. It can be used throughout life as a protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids.
Phenylketonuria (PKU) is inherited, which means it is passed down through families. Both parents must pass on the defective gene in order for a baby to have the condition. This is called an autosomal recessive trait.
Babies with PKU are missing an enzyme called phenylalanine hydroxylase, which is needed to break down an essential amino acid called phenylalanine. The substance is found in foods that contain protein.
Without the enzyme, levels of phenylalanine and two closely-related substances build up in the body. These substances are harmful to the central nervous system and cause brain damage.
Taking supplements such as fish oil to replace the long chain fatty acids missing from a standard phenylalanine-free diet may help improve neurologic development, including fine motor coordination. Other specific supplements, such as iron or carnitine, may be needed.

18. Autosomal Recessive Tay Sachs Genotype: (chromosome 15) tt Expression:
Lack enzyme hexosaminidase A
Lipid accumulation in brain, blindness, mental deficiency, death
Treatment:
None
Genetic testing available

19. Autosomal Recessive Cystic Fibrosis Genotype: (chromosome 12) cc
Expression:
Deletion of 3 bases = loss of phenylalanine in gene
Abnormal chloride channels cannot be transported to membrane
No chloride channels causes airways to become clogged with thick mucous
Treatment
Drug therapies and lung therapies extend lives

20. Autosomal Dominant
Only one copy of the genes is necessary to exhibit the trait
Represented by a capital letter
Achondroplasia
Huntington’s Disease
Hypercholesterolemia

21. Autosomal Dominant Huntington Disease Genotype: (chromosome 4) Hh
Expression:
Extensive repetition of CAG on DNA
Adult-onset
Neurological Symptoms Include:
Disorientation or confusion, Loss of judgment, Loss of memory, Speech changes
Death (usually by 50)
Treatment
Medications used to slow symptoms
Guthrie’s wife founded the Huntington’s Disease Society of America in 1977 which funds and conducts research on HD
Singer/Songwriter Woody Guthrie
“This Land is Your Land”

22. Autosomal Dominant Achondroplasia (dwarfism) Genotype: (chromosome 4)Aa
Expression:
Problems with bone ossification of long bones
Effect growth
Average head and torso with shortened arms and legs
Fun Fact
80% of Achondroplasia cases are new mutations primarily from men >35
    Shown on the right are seven pseudoachondroplasic members of the Ovitz family, a family of Romanian Jews who toured eastern Europe as a musical troupe before World War II (their taller siblings working backstage), survived imprisonment at Auschwitz, and finally emigrated to Israel. They were photographed on arrival in Haifa in Their father was (apparently) of ordinary height and was twice married, both times to women of ordinary height. With his first wife, he had two affected daughters [possibly the two older women in flowered dresses], and with his second five affected children (three girls and two boys) shown here, as well as three children of ordinary height. This suggests the father had a germline mutation p P, in which case the expected ratio from Pp x pp 50% "P" : 50% "p", as compared with the observed ratio of 7 affected : 3 unaffected children. Note that this departure from expectation is the same ratio of girls to boys. [Homework: test the ratios by chi-square and 2x2 contingency tests]. The sons are reported to have had taller children (Pp x pp 50% "pp"); the daughters were unable to bear children because of their narrow pelvises

23. Codominant 2 alleles can be expressed at the same time
Sickle Cell Anemia
HA – normal allele
HS - sickle cell
HA HA , HA HS, HS HS

24. Sickle Cell Anemia HA HA HA HS HS HS Normal Sickle Cell Trait
Sickle Cell Disease
Normal Hemoglobin
Both normal and abnormal hemoglobin
Abnormal hemoglobin
Normal rbc shape
Normal and sickle shape
Sickle shaped rbc

25. Distribution of Sickle Cell Anemia vs. Malaria
10% of African Americans and
40% of populations in Africa and Asia carry the gene for Sickle Cell Anemia

26. From gene to molecule DNA normal hemoglobin
CAC GTG GAC TGA GGA CTC CTC
mRNA
Amino acid sequence (p303)
DNA Sickle Cell Anemia
CAC GTG GAC TGA GGA CAC CTC
amino acid
GUG CAC CUG ACU CCU GAG GAG
Val – His – Leu – Thr – Pro – Glu – Glu…
…146
GUG CAC CUG ACU CCU GUG GAG
Val – His – Leu – Thr – Pro–VAL – Glu…
…146

27. Sex-Linked Genes
Genes that are found on the X (or Y) chromosome and are linked to a person’s gender.
Recessive type seems to disappear only to reappear later.
Males have a higher chance of having sex-linked disorders.
They only need one copy of the gene in order to express it.
Examples: colorblindness, hemophilia, Duchenne Musclar Dystropy

28. Sex-linked Recessive Red-Green Colorblindness Normal Vision
would be able to see all #s
XCXC, XCXc
XCY
A colorblind person
could see 25 and 56
XcXc
XcY

29. Sex-linked Recessive
Red-Green Colorblindness

30. Sex-linked Recessive Hemophilia Genotype: XhXh, XhY carrier: XHXh
Expression:
Lack of clotting factors for blood
Bleeder’s disease
Can die if bleeding is left untreated
Treatment:
Clotting factor replacement
Gene therapy* (what is gene therapy?)
The transplantation of normal genes into cells in place of missing or defective ones in order to correct genetic disorders. Gene therapy works by a normal gene is placed where a missing or defective gene is to try and fix the problem. Gene therapy is used in Hemophilia. 

31. Royal Family and Hemophilia

32. Sex-linked Recessive Duchenne Muscular Dystrophy Genotype: XmXm, XmY
carrier: XMXm
Expression:
Defective protein in muscle (dystrophin)
Fatigue
Learning difficulties (IQ can be below 75)
Muscle weakness
Eventually, inability to walk and breathe
Death by 25
Treatment:
Steroid drugs and supplements
Working on gene therapy

33. X-inactivation Females have 2 copies of X
One is randomly turned off early in development
Different cells have different Xs active

34. Chromosomal Disorders
Rather than 1 gene effecting one protein an entire chromosome is deleted or added.
Cause:
Non-disjunction of chromosomes (autosomes or sex chromosomes) during meiosis
Examples: Down Syndrome, Turner’s Klinefelter’s

35. Homologous chromosomes fail to separate
Nondisjunction
Section 14-2
Homologous chromosomes fail to separate
Meiosis I:
Nondisjunction
Meiosis II
Go to Section:

36. Homologous chromosomes fail to separate
Nondisjunction
Section 14-2
Homologous chromosomes fail to separate
Meiosis I:
Nondisjunction
Meiosis II
Go to Section:

37. Homologous chromosomes fail to separate
Nondisjunction
Section 14-2
Homologous chromosomes fail to separate
Meiosis I:
Nondisjunction
Meiosis II
Go to Section:

38. Chromosomal Disorder Down Syndrome Genotype: (autosomal) 47 XX +21
Expression:
Non-disjunction of chromosome 21
Mental retardation, growth failure, intestinal and heart problems, leukemia, early onset Alzheimer’s
Treatment:
No specific treatment

39. Incidence of Down’s Syndrome and mother’s age

40. Chromosomal Disorders
Non disjunction of sex chromosomes leads to extra of loss of an X or Y chromosome

41. Chromosomal Disorders
Turner’s Syndrome
Genotype: (sex chromosome)
45 XO
Expression:
Female
Sterile
Sex organs do not fully develop during puberty
Treatment
Growth hormone treatment, estrogen treatment

42. Chromosomal Disorders
Klinefelter’s Syndrome
Genotype: (sex chromosome)
48 XXXY
Expression:
Male
Sterile
Breast growth
Language problems
Lower energy
Treatment
Testosterone replacement, speech therapy, breast reduction, physical therapy