Lecture 6 - Chapter 6

Page 1: Pedigree Analysis Introduction

  • Discussion about Luke and a mention of a sister, implying family lineage and connection to Skywalker

  • Importance of genealogy and analyzing family backgrounds


Page 2: Weekly Class Plan

  • Today: Lecture on Chapter 6

  • Tuesday: Discussion for week 4

  • Wednesday: Focus on genetics in research and the Brenner paper

  • Friday: Homework related to Chapter 6

  • Sunday: Wikipedia check-in 1 (20 points) – requiring six trainings completed and evaluating an article

  • Monday: Exam 1

  • Tuesday: Group discussions on Wikipedia topics


Page 3: Dihybrid Cross Review

  • Interactions between two genes and their impact on phenotypic ratios:

    • No interaction: 9:3:3:1

    • Novel phenotypes: 9:3:3:1

    • Duplicate and novel: 9:6:1

    • Recessive epistasis: 9:4:3

    • Dominant epistasis: 12:3:1

    • Duplicate recessive epistasis: 9:7

    • Duplicate dominant epistasis: 15:1

    • Dominant and recessive epistasis: 13:3

  • Concept of genetic pathways: Understanding the difference between mutant phenotypes and their normal functions by analyzing double mutants


Page 4: Pedigree Analysis in Human Genetics

  • Learning Goals:

    • Utilize concordance measurements and adoption studies to compare genetic and environmental contributions to phenotypes

    • Create comprehensive pedigrees for traits and calculate genetic outcomes

    • Predict genetic trait nature from inheritance patterns observed in pedigrees

    • Discuss cytoplasmic and gender-linked inheritance patterns


Page 5: Complexity in Human Genetics

  • Human genetics presents more complexity compared to model organisms

    • Lack of true breeding or isogenic individuals

    • Difficulty in controlling matings

    • Overall abundance of data points complicating genetic analysis


Page 6: Genetics vs Environment

  • Inquiry into traits influenced by genetics, environment, or both

    • Difference between monozygotic (identical) and dizygotic (fraternal) twins

    • Dizygotic twins share about 50% genetic information

    • Concordance measures percentage of twins sharing the same phenotype, typically assessed through twin/adoption studies

    • Higher concordance in monozygotic twins indicates strong genetic influence; similar levels in dizygotic twins suggest environmental impact


Page 7: Understanding Concordance

  • Questions regarding factors not driven by genetics

  • Identifying numerical indicators for entirely genetic or entirely environmental diseases


Page 8: Insights from Adoption Studies

  • Adoption studies often involve children adopted as babies by unrelated individuals

  • Importance of gathering biological parent data, despite limiting study pool

  • Findings from such studies may indicate genetic influence if there's a discrepancy between outcomes in adoptive and biological contexts


Page 9: Pedigree Analysis - Individuals

  • Key symbols for individuals in pedigree charts:

    • Gender identification: Male, Female, Unspecified

    • Definitions:

      • Unaffected person

      • Affected person with the trait

      • Obligate carrier (carries the gene without expressing the trait)

      • Asymptomatic carrier (unaffected currently but can express trait later)

      • Proband (first affected family member observed by a geneticist)

      • Deceased person

      • Family history unknown


Page 10: Pedigree Analysis - Families

  • Description of a family with two girls and one boy in order of birth

  • Notation for adoption, twins, and consanguinity (relation between mating individuals)

    • Notations include different symbols and lines to indicate relationships


Page 11: Pedigree Analysis - Generations

  • Generational labeling: Roman numerals for generations, Arabic numerals for individuals within those generations

  • Identification focus: Who is circled in the pedigree


Page 12: Creating a Pedigree Example

  • Example of Todd and Jane planning a family linked to Tay Sachs disease (autosomal recessive)

  • Importance of constructing a complete pedigree and calculating the probability of disease in offspring


Page 13: Predicting Genetics via Pedigrees

  • Analysis of Fig 6.3 in the textbook focusing on:

    • Disease phenotype indicators in a pedigree

    • Generation skipping

    • Equal effects on males and females

    • Paternal transmission of traits


Page 14: Assumptions in Pedigree Analysis

  • Common patterns observed:

    • Diseases tend to inherit rather than arise as new mutations

    • Disease alleles typically rare

    • Phenotypes often linked to single genes with full penetrance

    • Use of OMIM (Online Mendelian Inheritance in Man) as a resource for genetic traits with vast databases


Page 15: Analyzing Inheritance Patterns

  • Examination of Fig 6.4 regarding inheritance patterns

    • Questions of skipping generations, equal gender distribution, and paternal transmission


Page 16: Sex-Linked Genes: Y Chromosome

  • Examination of inheritance patterns specific to the Y chromosome along with related analysis questions


Page 17: Sex-Linked Genes: X Chromosome

  • Similar to Y chromosome analysis but focuses on X-linked patterns


Page 18: Practice Questions on Inheritance Patterns

  • Engaging with practice scenarios to predict inheritance patterns and their characteristics


Page 19: More Practice on Inheritance Predictions

  • Continuation of practice exercises emphasizing inheritance patterns


Page 20: Cytoplasmic Inheritance

  • Majority of DNA is in chromosomal pairs, but mitochondria contain distinct DNA

  • Mitochondrial traits typically inherited from mothers, impacting both daughters and sons

  • Mitochondria distribution during cell division can be uneven, causing varying outcomes in progeny

  • Mitochondrial diseases impact approximately 1 in 5000 and can lead to severe health conditions


Page 21: Leber Hereditary Optic Neuropathy (LHON)

  • Characteristics of LHON linked to mitochondrial mutations:

    • Expected patterns of inheritance and disease presentation

    • Assessment query about true/false statements regarding the disease's inheritance patterns


Page 22: Review of LHON Patterns

  • Continued assessment and understanding of LHON characteristics through True/False disambiguation


Page 23: Characteristics Influenced by Sex

  • Insight into sex-influenced characteristics that show higher penetrance in one sex compared to the other

    • Examples illustrating autosomal versus X-linked resemblance


Page 24: Exploring More Sex-Influenced Traits

  • Analysis integrating X-linked analogies to sex-influenced characteristics across generations


Page 25: Sex-Limited Characteristics

  • Traits displayed exclusively by one sex, exemplified by precocious puberty (autosomal dominant)

  • Analysis of inheritance in male offspring versus female carriers


Page 26: Comparison of Genetic Definitions

  • Difference between sex-influenced, sex-limited, and sex-linked characteristics:

    • Sex-influenced and sex-limited traits are autosomal, whereas sex-linked traits reside on sex chromosomes


Page 27: Genetic Maternal Effect

  • Discussion of how maternal genetics influence offspring phenotypes prior to embryo DNA transcription

  • Example allele dominance (Dextral S+) impacting traits


Page 28: Genomic Imprinting Concept

  • Explanation of the significance of parental allele lineage in expressions of certain genes (Igf2).

  • Discussion on the resetting of DNA marks during gamete formation


Page 29: Genomic Imprinting Outcomes

  • Expected genetic outcomes when mating individuals with functional/nonfunctional Igf2 alleles


Page 30: Continuing Genomic Imprinting Outcomes

  • Expected outcomes in mating scenarios and potential offspring phenotypes


Page 31: Influence of Sex on Heredity

  • Summary of how various genetic phenomena define characteristics influenced by sex:

    • Sex-linked: Genes on sex chromosomes

    • Sex-influenced: Autosomal genes more expressed in one sex

    • Sex-limited: Autosomal traits expressed in only one sex

    • Genetic maternal effect: Determination by maternal genotype

    • Cytoplasmic inheritance: Largely inherited from one parent

    • Genomic imprinting: Expression affected by transmitting parent sex


Page 32: Practice Scenario on Inheritance

  • Evaluates probabilities of affected children from specific parental unions and genetic trait carriers


Page 33: Sample Issues with Practical Application

  • Scenario considerations regarding horn traits in male and female populations, and additional traits in the Lesser Whatsit species


Page 34: Pedigree Analysis Fig 6.7

  • Visual representation accompanying discussions, detailing affected individuals across generations


Page 35: Pedigree Analysis Fig 6.10

  • Final visual representation highlighting the generational impact of genetic diseases or traits