Genetic Principles - Washington University Genetics

Genetic Principles ADVANCED GENETICS COURSE, BIO 5491

15 JANUARY 2020

SADIE VANHORN, TA

Mendel: the father of geneticsEstablished 2 Principles

1. Law of Segregation: alleles are independently separated into gametes

2. Law of Independent Assortment: alleles from different genes assort independently during gamete formation

Rr

R r

Parent

Gamete

Image: epxii

While famous for peas, Mendel

also studied →Images - left to right, top to bottom: Wikimedia Commons, Pinterest, Time Magazine, Wikimedia Commons, WorldOfFloweringPlants.com, WorldOfFloweringPlants.com

Hieracium, aka Hawkweed Mirabilis, aka Jalapa flowers

Honeybees Maize

Cirsium, aka Thistle Geum, aka Avens

Mendel’s experimental procedure1. Define phenotype

2. Separate generations

3. Quantitative and statistical relationships

This was very effective!

Simple ratio interpretation

Follow-up experiments also fell into expected ratios

How probable were Mendel’s experiments?Fisher: are the counts too good to be true?

1. 6022:2001 is very close to an exact 3:1 ratio

2. The probability of a fit this this close, by chance is 0.00007

3. Possible that Mendel had a larger sample size than was reported and results were cherry-picked.

Further statistical investigation▪Other investigators have repeated Mendel’s experiments and report rations closer and further than Mendel’s

▪Overall impression: results fit just fine with expectation.

Muller’s mutation experiments – what are the origins of genes and variation?

Main questions:

1. Do new genes arise (i.e. de novo mutations), or is all genetic variability preexisting?

2. Originally there was a “presence and absence” hypothesis, stating that genes loss is the cause for new phenotypes. This was supported as recently as 1914

←Hermann Muller

Image: genetics.org

Types of mutations1. Autosomal recessive mutations are

harder to study in diploid organisms due to the necessity of two recessive alleles to be present

2. Autosomal dominant and sex-linkedmutations are easier to study in diploid organisms

Muller’s experimental designEstablished quantitative study of mutations:

1. Objective index of mutations

2. A class of mutations that occurs frequently enough to give statistically significant values

Image: prettysmartscience.com

Sex-linked lethality and balancer chromosomesClB chromosome is a balancer for the Drosophila X chromosome

▪Balancers have large inverted sequences = no Crossing over

▪Includes a recessive lethal gene = no male flies (single X)

▪Dominant marker gene = “Bar” mutation

Ionizing radiation induces mutations

MULLER

Drosophila

X-rays

Affects germline and soma

STADLER

Barley

X-rays and radium exposure

Affects germline and soma

Both found a linear relationship between dosage and mutation rate

Sutton: chromosomes and heredity▪Observed that chromosomes follow Mendel’s principles – laws of segregation and independent assortment

▪Alleles may correspond to a part of a chromosome

▪Logically, they could only be a part of a chromosome, otherwise the number of allelomorphs would not exceed the number of chromosomes.

Bateson’s 3 types of non-Mendelian inheritance

1. Blended inheritance: multiple genes influencing a trait

2. First crosses that breed true: gametes of self-fertilizing species do not have reduction division

3. “False hybrid”: loss of a set of parental chromosomes in the offspring, creating a haploid organism (parthenogenesis)

Sutton’s contribution to geneticsChromosomal theory of inheritance

▪Definition: chromosome are the physical basis of genetic inheritance

▪Described how random assortment fulfills Mendel’s laws and explains variation in traits

1. Chromosomes are positioned independently

2. Homologous chromosomes segregate away

3. If multiple traits are on the same chromosome, they are inherited together or linked

Punnett squaresGenerations: P0 (parental), F1 (first generation progeny)

P0

▪Genotype: Bb

▪Phenotype: Red

F1

▪Genotype- BB:Bb:bb▪ Genotypic ratio: 1:2:1

▪Phenotype: Red:white▪ Phenotypic ratio: 3:1

Vocabulary!

Genetics vocabularyHOMOZYGOUS

the two alleles at a locus are identical

HETEROZYGOUS

the two alleles at a locus are different

Image: expii

Genetics vocabularyANEUPLOIDY

the presence of an abnormal number of chromosomes

Genetics vocabularyLINKAGE

the close proximity of two or more loci on a chromosome

LINKAGE DISEQUILIBRIUM

the non-random association of alleles at two or more loci that descend from a single, ancestral chromosome

Genetics vocabularySYNTENY

the conservation of blocks of order within two chromosomes that are being compared, usually between species

Genetics vocabularyEXPRESSIVITY

the degree to which a phenotype is displayed in individuals of a given genotype

PENETRANCE

the percentage of individuals of a given genotype that display a phenotype above the cutoff

Image: mun.ca

Genetics vocabularyPLEIOTROPY

a single gene may contribute to multiple phenotypes

EPISTASIS

a gene may interact with or modify the phenotype of another gene

A BC

Genetics vocabularyEPIGENETICS

heritable (through mitosis or meiosis) changes in gene regulation rather than changes in the DNA sequence itself

Genetics vocabularyINHERITANCE

the way in which genes are passed to the next generation

HERITABILITY

the proportion of the parental phenotypic variance passed on genetically to the offspring

Genetics vocabularyHARDY-WEINBERG EQUILIBRIUM

in the absence of evolutionary influences (selection, drift, migration, etc.), the genotype and allele frequencies in a population will remain constant

Image: khanacademy

Genetics vocabularyEVOLUTION

the change in the frequency of alleles in a population over time

Image:boundino.github.io