Chapter 9 Key Knowledge: patterns of inheritance in sexually reproducing organisms: one gene locus, monohybrid cross including dominance, recessiveness, co-dominance; multiple alleles, two gene loci: dihybrid cross, pedigree analysis: autosomal, sex-linked inheritance, test cross.

Basic Concepts of Inheritance Diploid organisms One gene two alleles both alleles equally viable Exception More than two alleles at one gene (e.g. ABO blood system) Lethal genotypes (e.g. Manx cats can only be heterozygous [Mm] because the homozygous dominant genotype [MM] is lethal).

The Eight Steps The Punnett Square Analysis of Inheritance

1. Set up Genetic Hypothesis 2. Assign Alleles 3. Show P phenotypes 4. Show P genotypes 5. Show P ova/sperm punnet square 6. Show F 1 genotypes and frequencies 7. Show F 1 phenotypes and percentages 8. Answer the question The Eight Steps

1.Set up Genetic Hypothesis Number of genes Number of alleles per gene Which allele is dominant and which allele is recessive e.g. 1 gene, 2 alleles, red allele is dominant to white allele The Eight Steps

2. Assign Allele symbols R = Dominant red colour allele r = recessive white colour allele The Eight Steps

3. Show P (parental) phenotypes Red coloured flowers × Red coloured flowers The Eight Steps

4. Show P genotypes Rr × Rr The Eight Steps

5. Show P ova/sperm punnett square The Eight Steps Rr RRRRr r rr

6. Show F 1 (Filial) genotypes and frequencies ¼RR : ½Rr : ¼rr The Eight Steps

7. Show F 1 phenotypes and percentages 75% red coloured flowers and 25% white coloured flowers The Eight Steps

8. Answer the question There will be 75% red coloured flowers and 25% white coloured flowers The Eight Steps

1. Set up Genetic Hypothesis 2. Assign Alleles 3. Show P phenotypes 4. Show P genotypes 5. Show P ova/sperm punnet square 6. Show F 1 genotypes and frequencies 7. Show F 1 phenotypes and percentages 8. Answer the question The Eight Steps

Monohybrid crosses Hypothesis: one gene and two alleles, round is dominant to wrinkled

Dihybrid crosses Hypothesis: two genes each with two alleles, green is dominant to yellow and round is dominant to wrinkled The Punnett square on the right shows the resulting genotypes when two heterozygous parents with RrYy genotype are crossed together.

Test crosses A test cross may be used for either a monohybrid cross or a dihybrid cross. Test crosses are carried out in order to determine the unknown genotype of an individual. In order to do a test cross, the individual is mated with a homozygous recessive individual (aa or aabb). The frequency of phenotypes of the progeny are then analysed in order to determine the genotype of the individual being tested.

Multiple Alleles The ABO blood group system is the most important blood type system in human blood transfusion. ABO blood types are also present in three other great apes (chimpanzees, bonobos and gorillas) Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene) on the long arm of chromosome 9 (9q34). The gene has three different alleles: i, I A and I B. i codes for O blood type, I A for A blood type and I B codes for B blood type. An individual can only carry two of the three alleles.

Multiple Alleles The gene has three alleles: i, I A and I B. i codes for O blood type, I A for A blood type and I B codes for B blood type. The i allele is recessive to both the I A and I B alleles The I A allele and I B alleles are codominant GenotypePhenotype IAIAIAIA A IAiIAiA IBIBIBIB B IBiIBiB IAIBIAIB AB iiO

Linked Genes Genetic linkage is a term which describes the tendency of certain loci (genes) to be inherited together. Loci on the same chromatid are physically close to one another and tend to stay together during meiosis and are thus genetically linked (i.e. they do not assort independently of each other).

Reading pedigrees Males represented by squares Females represented by circles. Filled in squares or circles indicate that the individual has the condition Patterns of inheritance often indicate the mode of inheritance

Pedigree Symbols Female (Unaffected) Male (Unaffected) Female (Affected) Male (Affected) Female (Carrier) Male (Carrier) Female (Unaffected Deceased) Male (Unaffected Deceased)

Nomenclature of a Human Pedigree If possible, male partner should be placed left of female partner on relationship line. I II Siblings should be listed left to right in birth order (oldest to youngest). Relationship Line Sibship Line Line of Descent Individual’s Line 123 Individual within Generation Generation (Roman Numerals)

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Modes of Inheritance There are four modes of inheritance Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Each of these four modes of inheritance can be deciphered from a pedigree.

Autosomal Recessive Inheritance Usually there is no previous family history The most likely place to find a second affected child is a sibling of the first

Autosomal Recessive Inbreeding increases the chance of observing an autosomal recessive condition E.g. Cystic fibrosis, sickle cell anaemia, Tay Sachs disease.

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Cystic Fibrosis Cystic fibrosis is the most common lethal genetic disorder among Caucasians. A chloride ion (Cl - ) transport protein is defective in affected individuals. Normally when a chloride ion passes through a membrane, water follows. In cystic fibrosis patients, a reduction in water results in a thick mucus which accumulates in bronchial passageways and pancreatic ducts.

Phenylketonuria (PKU) Individuals with phenylketonuria lack an enzyme needed for the normal metabolism of phenylalanine, Coded by a gene on chromosome 12. Newborns are regularly tested for elevated phenylalanine in the urine. If the infant is not put on a phenylalanine-restrictive diet in infancy until age seven when the brain is fully developed, brain damage and severe mental retardation result.

Autosomal Dominant Inheritance All affected individuals should have an affected parent Both sexes should be equally affected Roughly 50% of the offspring of an affected individual should also be affected e.g. Huntington’s disease, achondroplastic dysplasia (dwarfism), Neurofibromatosis.

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Huntington’s Disease Individuals with Huntington’s disease experience progressive degeneration of the nervous system and no treatment is presently known. Most patients appear normal until middle age. The gene coding for the protein huntingtin contains many more repeats of glutamines than normal.

Huntington’s disease

X-linked Recessive Gene located on the X chromosome More males than females affected (X a Y) (males have only one X from mother) Females can only be affected if the father is affected and mother is a carrier (heterozygous) or affected (homozygous) An affected female (X a X a ) will pass the trait to all her sons and daughters will be carriers if father is not affected Males cannot be carriers (only have one X so either affected or not) Can skip generations e.g. colour blindness, haemophilia, Duchene muscular dystrophy

Trait is rare in pedigree Trait skips generations Affected fathers CANNOT pass to their sons Males are more often affected than females X-linked Recessive Pedigrees

X-linked Dominant Dominant gene on X chromosome Affected males pass to all daughters and none of their sons: Genotype= X B Y If the mother has an X-linked dominant trait and is homozygous (X B X B ), all children will be affected If Mother heterozygous (X B X b ) 50% chance of each child being affected e.g. Fragile X syndrome, Vitamin D resistant rickets, brown teeth enamel.

Trait is common in pedigree Affected fathers pass to ALL of their daughters Males and females are equally likely to be affected X-linked Dominant Pedigrees

X-linked dominant diseases are extremely unusual. Often, they are lethal (before birth) in males and only seen in females in heterozygous form. Homozygous dominant genotype is usually lethal X-linked Dominant Diseases

Problems...

What is the pattern of inheritance? What are IV-2’s odds of being a carrier?

Sample pedigree - cystic fibrosis What can we say about I-1 and I-2? What can we say about II-4 and II-5? What are the odds that III-5 is a carrier?

What is the inheritance pattern? What is the genotype of III-1, III-2, and II-3? What are the odds that IV-5 would have an affected son?

III-1 has 12 kids with an unaffected wife 8 sons - 1 affected 4 daughters - 2 affected Does he have reason to be concerned about paternity?