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Patterns of InheritanceChapter 9Key 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 InheritanceDiploid organismsOne genetwo allelesboth alleles equally viableExceptionMore 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 StepsThe Punnett Square Analysis of InheritanceSet up Genetic HypothesisAssign Alleles Show P phenotypesShow P genotypesShow P ova/sperm punnet squareShow F1 genotypes and frequenciesShow F1 phenotypes and percentagesAnswer the question

The Eight StepsSet up Genetic HypothesisNumber of genesNumber of alleles per geneWhich allele is dominant and which allele is recessivee.g. 1 gene, 2 alleles, red allele is dominant to white alleleThe Eight StepsAssign Allele symbolsR = Dominant red colour allele r = recessive white colour allele

The Eight StepsShow P (parental) phenotypesRed coloured flowers Red coloured flowersThe Eight StepsShow P genotypesRr RrThe Eight StepsShow P ova/sperm punnett squareThe Eight StepsRrRRRRrrRrrr

Show F1 (Filial) genotypes and frequenciesRR : Rr : rrThe Eight StepsShow F1 phenotypes and percentages75% red coloured flowers and 25% white coloured flowersThe Eight StepsAnswer the questionThere will be 75% red coloured flowers and 25% white coloured flowersThe Eight StepsSet up Genetic HypothesisAssign Alleles Show P phenotypesShow P genotypesShow P ova/sperm punnet squareShow F1 genotypes and frequenciesShow F1 phenotypes and percentagesAnswer the question

The Eight StepsMonohybrid crossesHypothesis: one gene and two alleles, round is dominant to wrinkled

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

Test crossesA 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 AllelesThe 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, IA and IB. i codes for O blood type, IA for A blood type and IB codes for B blood type.An individual can only carry two of the three alleles.Multiple AllelesThe gene has three alleles: i, IA and IB. i codes for O blood type, IA for A blood type and IB codes for B blood type.The i allele is recessive to both the IA and IB allelesThe IA allele and IB alleles are codominant

GenotypePhenotypeIAIAAIAiAIBIBBIBiBIAIBABiiOLinked GenesGenetic 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 pedigreesMales represented by squaresFemales represented by circles. Filled in squares or circles indicate that the individual has the conditionPatterns of inheritance often indicate the mode of inheritancePedigree SymbolsFemale (Unaffected)Male (Unaffected)Female (Affected)Male (Affected)Female (Carrier)Male (Carrier)Female (Unaffected Deceased)Male (Unaffected Deceased)Nomenclature of a Human PedigreeIf possible, male partner should be placed left of female partner on relationship line.IIISiblings should be listed left to right in birth order (oldest to youngest).Relationship LineSibship LineLine of DescentIndividuals Line123Individual within GenerationGeneration(Roman Numerals)23-23

Modes of InheritanceThere are four modes of inheritanceAutosomal dominantAutosomal recessiveX-linked dominant X-linked recessive

Each of these four modes of inheritance can be deciphered from a pedigree.Autosomal Recessive InheritanceUsually there is no previous family historyThe most likely place to find a second affected child is a sibling of the first

25Autosomal RecessiveInbreeding increases the chance of observing an autosomal recessive conditionE.g. Cystic fibrosis, sickle cell anaemia, Tay Sachs disease.

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27Autosomal recessive disorders have these characteristics:Affected children can have unaffected parents.Heterozygotes (Aa) have a normal phenotype.Two affected parents will always have affected children.Affected individuals with homozygous dominant mates will have unaffected children.Close unaffected relatives who reproduce are more likely to have affected children if they have joint affected relatives.Both males ad females are affected with equal frequency.How would you know the individual at the asterisk is heterozygous?Cystic FibrosisCystic 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.28Genetic testing for the CF gene is possible.

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 InheritanceAll affected individuals should have an affected parentBoth sexes should be equally affectedRoughly 50% of the offspring of an affected individual should also be affectede.g. Huntingtons disease, achondroplastic dysplasia (dwarfism), Neurofibromatosis.

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32Autosomal dominant disorders have these characteristics:Affected children will have at least one affected parent.Heterozygotes (Aa) are affected.Two affected parents can produce an unaffected child.Two unaffected parents will not have affected children.Both males and females are affected with equal frequency.How would you know the individual at the asterisk is heterozygous?Huntingtons DiseaseIndividuals with Huntingtons 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. 33The gene for Huntington disease is located on chromosome 4.Huntingtons disease

34Persons with this condition gradually lose psychomotor control of the body. At first, the disturbances are only minor, but the symptoms become worse with time.X-linked RecessiveGene located on the X chromosomeMore males than females affected (XaY) (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 (XaXa) will pass the trait to all her sons and daughters will be carriers if father is not affectedMales cannot be carriers (only have one X so either affected or not)Can skip generationse.g. colour blindness, haemophilia, Duchene muscular dystrophy35Trait is rare in pedigreeTrait skips generationsAffected fathers CANNOT pass to their sonsMales are more often affected than females

X-linked Recessive Pedigrees

X-linked DominantDominant gene on X chromosomeAffected males pass to all daughters and none of their sons: Genotype= XBYIf the mother has an X-linked dominant trait and is homozygous (XBXB), all children will be affectedIf Mother heterozygous (XBXb) 50% chance of each child being affected e.g. Fragile X syndrome, Vitamin D resistant rickets, brown teeth enamel.37Trait is common in pedigreeAffected fathers pass to ALL of their daughtersMales 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 lethalX-linked Dominant Diseases

Problems...What is the pattern of inheritance?What are IV-2s 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 affected4 daughters - 2 affected

Does he have reason to be concerned about paternity?