Dihybrid crosses and Patterns of inheritance (pedigrees) Lesson 5.

Learning Goals

Dihybrid cross genetic diagram P Phenotypes Round Yellow seed X Wrinkled Green seed (Pure bred) Genotypes RRYY rryy meiosis Gametes RY ry fertilisation F1 RrYy (Selfed) Round Yellow Proportions 100%

A dihybrid cross can be treated as two separate monohybrid crosses The expected probability of each type of seed can be calculated: Probability of an F2 seed being round = 75% or ¾ Probability of an F2 seed being wrinkled = Probability of an F2 seed being yellow = Probability of an F2 seed being green =

A dihybrid cross can be treated as two separate monohybrid crosses The expected probability of each type of seed can be calculated: Probability of an F2 seed being round = 75% or ¾ Probability of an F2 seed being wrinkled = 25% or ¼ Probability of an F2 seed being yellow = 75% or ¾ Probability of an F2 seed being green = 25% or ¼

THE LAW OF INDEPENDENT ASSORTMENT It appears that the inheritance of seed shape has no influence over the inheritance of seed colour The two characters are inherited INDEPENDENTLY The pairs of alleles that control these two characters assort themselves independently

Mendel & Meiosis The pairs of chromosomes could orientate in different ways at Anaphase 1

Patterns of Inheritance

Pedigrees A pedigree is a genetic family tree that shows how prevalent a trait is in a family unit from generation to generation. They are often used to track the expression of genetic conditions and disorders.

Pedigrees Squares represent males and circles females. A coloured in shape means that person has the trait in question. A half coloured in shape means that they are carrying an allele for a recessive trait.

Anatomy of a Pedigree Male (left) Female (right) Affected individuals Carriers (Heterozygotes for autosomal recessive) Deceased individuals Sex unspecified Male (left) Female (right)

Autosomal Dominant Inheritance Autosomal means not on the sex chromosomes. Refers to those situations in which a single copy of an allele is sufficient to cause expression of a trait.

Autosomal Dominant Inheritance 1. Every affected person should have at least one affected parent. 2. Males and females should be equally often affected. 3. An affected person has at least a 50% chance of transmitting the dominant allele to each offspring.

Characteristics of a Dominant Pedigree An affected individual has at least one affected parent As a result, dominant traits show a vertical pattern of inheritance the trait shows up every generation Two affected individuals may have unaffected children A a Assume trait isn’t happening spontaneously. How is this possible? (last pt) AA Aa aa A a a 15

Autosomal Dominant Inheritance examples Progeria (caused by a mutation) in which the person ages very rapidly. They die before they can reproduce. Huntington’s Disease in which the central nervous system starts to break down around the age of 30.

Autosomal Recessive Inheritance Refers to those situations where two recessive alleles result in a trait being expressed.

Autosomal Recessive Inheritance 1. An affected person may not have affected parents. Parents would be carriers. 2. Affects both sexes equally. Can appear to skip generations. 3. Two affected parents will have affected children 100% of the time.

Characteristics of Recessive Pedigrees In pedigrees involving rare traits, a horizontal pattern of inheritance is observed the trait may not appear in every generation An individual who is affected may have parents who are not affected, particularly as a result of consagineous matings All the children of two affected individuals are affected a a aa a a

Autosomal Recessive Examples Albinism is a genetic condition which is the loss of pigment in hair, skin and eyes. Tay Sachs is a genetic disorder which is a build up of fatty deposits in the brain, eventually proving to be fatal. Cystic Fibrosis is the most common fatal genetic disorder. Mutation in chloride transport protein that causes thick mucus to build up in lungs

Pedigree of a family with some members showing Huntington disease

Huntington disease is

Huntington disease is

Genetic Tests Karyotype Fluorescence in situ hybridization (FISH) Details chromosomal abnormalities through fluorescent tags on chromosomes Gene testing Analyzes specific sequence of gene. i.e. breast cancer susceptibility gene BRCA1 and BRCA2 Biochemical testing Analyzes abnormal enzymes and proteins (Tay Sachs)

FISH

FISH

Genetic Test for Cystic Fibrosis In 1989 researchers at Sick Kids identified the gene for cystic fibrosis Gene was on chromosome 7 and named CFTR (cystic fibrosis transmembrane conductance regulator) Over 1600 possible mutations in CFTR! Genetic tests can identify mutations 85-90% of the time 1 in every 3600 children in Canada are born with CF

Genetic test for Huntington disease In 1983 the gene for Huntington disease called huntingtin was the first human disease-associated gene to be mapped to a chromosome In 1993 huntingtin gene was sequenced CAG repeats Current genetic test looks for CAG repeats (36-39 repeats necessary for disease)

Genetic Counselling If there is a family history of a disease, couples may consult a genetic counsellor Use pedigrees to determine genotypes of the family members Explains probability on passing on disease-causing allele to children

Issues with genetic screening Why carry out genetic screening at all? When is a test accurate and comprehensive enough to be used as the basis for screening? Once an accurate test becomes available at reasonable cost, should screening become required or optional? If a screening program is established, who should be tested? Should private companies and insurance companies have access to employees and client test results? What education needs to be provided regarding test results?

Gene Therapy: A future cure? Technique aimed at treating genetic disorders by introducing the correct form of the defective gene into a patient’s genome Copy of “normal” gene is inserted into a vector (usually viral DNA) Virus infects cells and delivers gene into chromosomes

Future of Gene Therapy Still in experimental stages due to two obstacles: immune response to viral vector and poor integration into target chromosome In 2000 St. Michael’s Hospital became performed Canada’s first gene therapy for treatment of heart disease; gene produced protein for stimulation of new blood vessels