PM-149 Lecture 6. Mendelian Genetics 2024-2025 Student Version PDF

Lecture 6 Mendelian Genetics  Learning Objectives To explain Mendel’s 2 Laws of Inheritance. To recognise other degrees of gene dominance and different forms of gene interactions. To recognise patterns of inheritance from family pedigrees. To recall examples of common genetic conditions...

Lecture 6 Mendelian Genetics  Learning Objectives To explain Mendel’s 2 Laws of Inheritance. To recognise other degrees of gene dominance and different forms of gene interactions. To recognise patterns of inheritance from family pedigrees. To recall examples of common genetic conditions and inheritance patterns.  Gregor Mendel Austrian Monk Discovered the basic principles of heredity Worked on peas for over 8 years Prior to Mendel, heredity was regarded as a "blending" process and the offspring were essentially a “dilution” of the different parental characteristics.  Mendel’s peas Mendel looked at seven traits or characteristics of pea plants:  Law No. 1: The Law of Segregation Monohybrid cross: a genetic cross between two organisms P Generation with different variations at one locus. (Parental) P = Parental generation (pure generation) F1 Generation (Hybrids) F1 = First filial generation; offspring from a genetic cross (hybrid offspring) F2 = Second filial generation of a genetic cross (F1 hybrids x F1 hybrids) P Generation (Parental) F1 Generation (Hybrids) Pp Pp Pp Pp F2 Generation Results in 3:1 ratio PP or Pp pp From these experiments: 1. For each character, an organism inherits two copies of a gene, one from each parent – Law of segregation (Law No. 1). 2. Alternative versions of genes (alleles) account for variations in inherited characteristics. 3. If the two alleles at a locus differ, then the dominant allele determines the organism's appearance; the recessive allele has no visible effect on the organism. Law No. 2: The Law of Independent Assortment Dihybrid Crosses: Considering whether two characteristics are passed down from parents independently to each other. Law of Independent assortment - the two alleles for a heritable character segregate during gamete formation and end up in different gametes https://www.youtube.com/watch?v=Y1PCwxUDTl8  Punnet Square to predict Crosses Domina nt PP P P p Pp Pp Recessi ve p Pp Pp pp Click this link to watch an explanation on how to perform a punnett square -https://www.youtube.com/watch?v=S8ex-zYZBMY The Test Cross: determines the genotype of the dominant organism X Domina Recessi nt ve PP or pp Pp ? Beyond Mendelian Genetics: Incomplete Dominance Mendel was lucky! Traits he chose in the pea plant showed up very clearly… One allele was dominant over another, so phenotypes were easy to recognise.  Beyond Mendelian Genetics Incomplete Dominance: - intermediate inheritance R r R R R Rr Rr rr r Co-Dominance: expression of both traits Forms of gene interactions Epistasis: When an unrelated gene modifies the phenotypic expression of another gene Pleiotropy: When one gene influences two or more seemingly unrelated phenotypic traits Polygenic: When one characteristic is controlled by two or more genes. Examples are height, skin colour, eye colour….. Epistasis – Alzheimer’s Disease Sporadic Alzheimer’s Disease has linked to mutations in ApoE4 gene. but not all individuals with ApoE4 developed Alzheimer's (it was not ‘fully penetrant’). Many studies have identified over 100 gene- gene interactions with ApoE4 that increase or decrease susceptibility to Alzheimer’s. Pleiotropy – Marfan Syndrome Affects ~1 in 5,000 people. Mutations in FBN1 Causes heart problems, hypermobility, limb elongation and eye problems. Polygenic Polygenic Disease - Cancer Assessing Pedigrees Family history is an important tool in risk assessment. Symbols used in Pedigrees ` ` Vertical line = Offspring Male Female Identical twins ` ` Person whose sex is not known or ` Deceased Non-identical twins ` ` Marriage/Relationship ` Half siblings with ` Consanguineous (Cousin) ` the same father ` Marriage Pairs 1-22 = Autosomes, same in men & women Pair 23 = Sex Chromosomes, determine sex  Key: Male Pedigrees Female Affected Carrier Autosomal Dominant Autosomal Dominant Example Conditions; Huntington’s Disease Inheritance Marfan Syndrome Tuberous Sclerosis A a a Aa aa a Aa aa 2:2 ratio = 50% risk of an affected child in each pregnancy  Key: Male Pedigrees Female Affected Carrier Autosomal recessive Autosomal Recessive Example Conditions; Inheritance Cystic Fibrosis Sickle Cell Anaemia Beta-Thalassemia Albinism A a A AA Aa a Aa aa Although rare, recessively inherited disorders can also be passed on by homozygous recessive and carrier parents (see below) A a a Aa aa a Aa aa 1:2:1 ratio = 25% risk of an affected child in each pregnancy Pedigrees X-linked Recessive  Example Conditions; X-Linked Recessive Inheritance Duchenne/Becker Muscular Dystrophy Red-Green Colour Blindness Haemophilia A (Factor VIII) Haemophilia B (Factor IX) X x X XX Xx y Xy Xy 2:2 ratio = 0%* risk of an affected child in each pregnancy X X x XX XX y Xy Xy 1:1:1:1 ratio = 25%* risk of an affected child in each  Example conditions: X-Linked Dominant Inheritance Fragile X Syndrome X-Linked Alport Syndrome x X X xX XX Y xY XY In males X X x xX xX Y XY XY 2:2 ratio = 50% risk of an affected child in each pregnancy Summary Autosomal recessive inheritance – cystic fibrosis, sickle cell disease Autosomal dominant inheritance – Huntington’s disease, Marfan’s syndrome X-linked recessive inheritance – Duchene muscular dystrophy, Haemophilia A X-linked dominant inheritance – Fragile X syndrome Other degrees of dominance - Incomplete - Codominance Forms of gene interactions - Pleiotropy