1. Patterns of Inheritance
Chapter 9
BIOL 1010
Patterns of Inheritance

2. GENETICS: the scientific study of heredity
Genome: complete set of an organism’s gene Gene: unit of heredity which codes for a protein
Siberian huskies: look alike because they share a similar genetic history
Thick double coat, well-insulated ears, great stamina
Inbreeding: purebreds tend to concentrate ‘bad’ genes (i.e. PRA)
A dog’s behavior is determined by its genes and by the environment
Nature versus nurture

3. Gregor Mendel: “Father of Modern Genetics”
Gained posthumous fame as the founder of genetics
Was the first person to analyze patterns of inheritance: “heritable factors”
Deduced the fundamental principles of genetics
Austrian scientist and Augustinian friar
Most famous for working with pea plant hybridization experiments in St. Thomas Abbey (geneticists have since ID’d the genes that controlled for traits Mendel used
Could completely control fertilization, short generation time, many offspring, easily identifiable traits
1866: Published work (seven years after Darwin’s Origin of Species)
Rejected at first; Darwin and other scientists unsuccessful at trying to explain inheritance
Not until the 1900’s that the importance of his work was realized
Research was experimentally and mathematically rigorous, has stood the test of time

4. Rules of Probability
Rule of Multiplication: probability of a compound event is the product of the separate probabilities of the independent events
P(A and B) = P(A)*P(B)
Rule of Addition: if events are mutually exclusive, then the probability of either/or is the sum of the separate probabilities of the independent events
P(A or B) = P(A) + P(B)
The probability of event A AND event B occurring is the chance of event A occurring multiplied by the chance of event B occuring
The probability of event A OR event B occurring is the chance of event A occurring added to the chance of event B occuring

5. Genetic Nomenclature
Heredity: transmission of traits from one generation to the next
Phenotype (Character): heritable feature (i.e. flower color) based on genotype (genetic makeup)
Trait: variant of a character
Wild-type: variant found most often in nature
True-breeding: purebred, offspring are identical to the parent
Hybrids: offspring of two different true-breeding parents
The seven characters of pea plants studied by Mendel
Wild-type: doesn’t necessarily mean dominant. (i.e. freckles, a dominant trait, is less frequent in humans than no freckles, which is recessive)

6. Inherited Traits in Humans: Controlled by a Single Gene
*Most other traits such as hair or eye color are multigenic (polygenic) traits

7. Genetic Crosses
Monohybrid Cross
P generation: two different pure-breeding parental plants
F1 hybrids: the first generation plants obtained from crossing two selected pure breeding plants.
F1 hybrids do not produce seed that is the same as the parent plants
F2 hybrids: second generation plants (result of self or cross fertilization of F1 hybrids

8. Monohybrid Cross
A monohybrid cross is a cross between purebred parents that differ in only one characteristic
F1 generation: all show the trait of one parent (i.e. purple flowers)
F2 generation: show the two traits of the parents in a 3:1 ratio (i.e. purple to white flowers)
Monohybrid Cross
Figure 9.5 Mendel's cross tracking one character (flower color). (Step 3)

9. Mendel’s Law of Segregation
There are alternate versions of genes
For each inherited character, an organism inherits two alleles, one from each parent
Homozygous: two identical alleles
Heterozygous: two different alleles
If the two alleles differ (the individual is heterozygous)
Dominant allele: determines the phenotype (character)
Recessive allele: no noticeable effect on the phenotype (character)
Law of segregation: A sperm or egg carries only one allele for each character because the allele pair segregates during meiosis
Based on Mendel’s observations, he came up with four hypotheses

10. Punnett Squares Show the results of random fertilization
Each axis shows possible alleles from each parent

11. Test Crosses: Determining Unknown Genotypes
Mating of an individual of dominant phenotype but unknown genotype to a homozygous recessive individual

12. Modern Genetics Modern genetics
Homologous chromosomes contain the same genes at the same loci but may contain different alleles (alternative forms of a gene)
Gene locus (plural-loci): specific location of a gene on the chromosome
Gene loci: BRCA1: 17q21.31 (long arm of chromosome 17, band 21, sub-band 31)

13. Dihybrid Cross
A dihybrid cross is a cross between purebred parents that differ in two characteristics
F1 generation: all show the dominant trait of the two characters
F2 generation: show four combinations of traits in a 9:3:3:1 ratio
Figure 9.5 Mendel's cross tracking one character (flower color). (Step 3)

14. Mendel’s Law of Independent Assortment
Each pair of alleles assorts independently of the other pairs of alleles during gamete formation (the inheritance of one character has no effect on the inheritance of another)
Based on Mendel’s observations, he came up with four hypotheses

15. Mendel’s Laws and Meiosis
Chromosome Theory of Inheritance: genes are located at specific loci on chromosomes and that the behavior of chromosomes during meiosis and fertilization accounts for inheritance patterns
Law of segregation: two allele pairs segregate into different gametes during meiosis
Law of Independent Assortment: each pair of alleles for a particular character segregate independently of each other
How can genes located on the same chromosome be assorted independently?

16. A family pedigree showing inheritance of free versus attached earlobes
Male
Female
Affected Male
Affected Female
Mating
between related individuals
A family pedigree showing inheritance of free versus attached earlobes

17. Some Autosomal Disorders in Humans
Recessive Disorders
Albinism (1/22,000)
Cystic fibrosis (1/1,800)
Phenylketonuria (1/10,000)
Sickle cell disease (1/500)
Tay Sachs disease (1/3,500)
Dominant Disorders
Achondroplasia (1/25,000)
Alzheimer’s disease (early onset)
Huntington’s disease (1/25,000)
Hypercholesterolemia (1/500)
Recessive alleles (even lethal) persist indefinitely in populations in heterozygous carriers
Albinism: lack of pigment in skin, hair and eyes
Cystic fibrosis: excess mucus in lungs, digestive tract, liver; increased susceptibility to infections, death in early childhood unless treated
-30,000 in US, 70,000 worldwide, 1/25 people are carriers
Phenylketonuria: lack enzyme necessary to break down phenylalanine; accumulation of phenylalanine in blood; lack of normal skin pigment, mental retardation unless treated
Sickle cell disease: sickled red blood cells; damage to many tissues
Tay Sachs disease: lipid accumulation in brain cells, mental deficiency, blindness, death in childhood
Achondroplasia: dwarfism
Alzheimer’s disease: mental deterioration; usually strikes late in life
Huntington’s disease: mental deterioration and uncontrollable movements; strikes in middle age
Hypercholesterolemia: excess cholesterol in blood; heart disease

18. Inbreeding Increases the Likelihood that a Recessive Trait will be Inherited
Inbreeding: mating between close blood relatives
Increases the likelihood of homozygosity of a recessive allele in children of inbred parents
Most genetic disorders are not evenly distributed across all ethnic groups
Result of prolonged isolation of certain populations Dd DD DD Dd DD Dd Dd Dd
Early inhabitants of Martha’s Vineyard (island off the coast of Massachusetts) letd to frequent marriages between close relatives
Frequency of an allele that caused deafness was high
Inbreeding in dogs: many purebreds have known genetic defects
Inbreeding in endangered species: not many mates to choose from
European ancestry: cystic fibrosis, phenylketonuria
Ashkenazi Jews: Tay Sachs disease
African ancestry: sickle cell disease
dd=deaf

19. Dominant Disorders
One allele is all that is required to cause the phenotype
i.e. Achondroplasia: dwarfism (homozygosity=lethal)
Dominant lethal alleles are rare in populations
i.e. Huntington’s disease: causes degeneration of the nervous system in middle age
Family with and without achondroplasia: Amy Roloff and husband Matt (unrelated form of dwarfism) have four children, one with achondroplasia, three without
Achondroplasia: dwarfism, head and torso develop normally, arms and legs are short
Fibroblast growth factor receptor 3 which causes an abnormality of cartilage formation leading to shortened bones
Why are dominant lethal alleles rare?

20. Genetic Testing Carrier screening Prenatal diagnostic testing:
i.e. amniocentesis
Newborn screening
Genealogical DNA testing
Predicting adult-onset disorders
Estimating risks of disease development
Confirmational diagnosis
Forensic/identity testing
About 200,000 new breast cancer cases are diagnosed each year
Approximately 10% of these are heritable; they run in families
There are options if the results of genetic testing show a positive result for a BRCA mutation
Genetic counseling: (interdisciplinary field between biology and psychology)
Prenatal Diagnostic Testing
Amniocentesis: physician removes ~2tsp of amniotic fluid with a needle for genetic testing
Chorionic villus sampling: physician collects some placental tissue for genetic testing
Newer methods: able to isolate fetal cells from mother’s blood
Ashkenazi Jewish ancestry: higher risk for Tay Sachs, Fanconi anemia, cystic fibrosis and others
Ethical issues?

21. Variations on Mendel’s Laws
Incomplete dominance: F1 has an appearance in between the two parental phenotypes
Codominance: both alleles are fully expressed in heterozygous individuals
Pleiotropy: single gene influences more than one character
Polygenic Inhertitance: additive effects of two or more genes on a single phenotype
Environmental Factors: non-genetic, non-hereditary factors that contribute to phenotype
Mendel was lucky he chose peas and not snapdragons
Environment: weight, skin color, health and fitness, etc.

22. An Example of Incomplete Dominance
Hypercholesterolemia
Hypercholesterolemia: gene that codes for LDL receptor is defective, cells unable to mop up excess LDL from blood
HH: normal individuals
Hh: blood cholesterol levels about 2x normal, may have heart attacks by mid-30s
hh: blood cholesterol levels about 5x normal, may have heart attacks as early as age 2

23. An Example of Codominance
ABO Blood Groups
ABO Blood Groups: three alleles for blood type, IA, IB and i
Clumping of donor blood cells can kill the recipient
What blood type is the universal donor?
What blood type is the universal acceptor?
Blood types: Out of 100 people
38 will be O positive
7 will be O negative
34 will be A positive
6 will be A negative
8 will be B positive
2 will be B negative
4 will be AB positive
1 will be AB negative

24. An Example of Pleiotropy
Sickle-Cell Disease
Sickle-cell disease: defective gene causes abnormal hemoglobin proteins
Sickle cells are rapidly destroyed by the body
Sickle cells don’t flow smoothly in blood and tend to clump and clog

25. An Example of Polygenic Inheritance
Skin Color
Skin color: controlled by at least three genes

26. Linked Genes
Thomas Hunt Morgan: In 1916, published a paper on genes in Drosophila melanogaster (fruit fly)
Found the recombinant frequency to be 17%, not 50%
Punnett square on expected outcomes assuming independent assortment (575) and compare with actual outcomes
Calculate recombination frequency (391/2300) and convert into cM (centiMorgans)
Why are recombination frequencies generally not over 50%

27. Linked Genes
Genetic recombination (crossing over): usually ensures that genes on the same chromosome still assort independently
Linked genes: genes so close together on a chromosome that they do not assort independently but tend to travel together
Linkage map: diagrams describing relative gene locations using recombination frequencies
The shorter the distance between two genes, the less likely a crossover event will happen between them

28. Sex Chromosomes and Sex-Linked Genes
Sex chromosomes: X and Y
XX  Female
XY  Male
Sex-linked gene: any gene located on a sex chromosome
X-linked genes: the X chromosome contains many more genes (~2000 genes) than the Y chromosome (~78 genes)
Sex-linked disorders: disorders associated with a defective gene found on a sex (usually X) chromosome
Why doesn’t the Y chromosome contain as many genes as the X chromosome?
Why are none of the Y chromosome genes necessary for survival?

29. Sex-Linked Disorders in Humans
Red-green color blindness: recessive X-linked trait
Is characterized by a malfunction of light-sensitive cells in the eyes.
Males are more likely to be color blind than females
Red-green colorblindness: individual with normal color vision can see 150+ colors; individuals with red-green colorblindness can see fewer than 25
Why are males more affected than females?
Doesn’t two X chromosomes present a dosage problem?
Calico cat example
Figure 9.30
Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings

30. Sex-Linked Disorders in Humans
Hemophilia: “The Royal Disease”
Sex-linked recessive blood-clotting trait that may result in excessive bleeding and death after relatively minor cuts and bruises
Figure 9.32 Hemophilia in the royal family of Russia.
Figure 9.32