Mendel & the Gene Idea

Campbell and ReeceChapter 14

Definitions

Character: observable, heritable feature that may vary among individuals in a population

Trait: 1 of 2 or more detectable variants in a genetic character

True-breeding: refers to organisms that produce offspring of the same variety over many generations of self-pollination

Hybridization: cross-breeding 2 true-breeding individuals

Mendel’s Experiments

Advantages of using peas:1. several characters with “either-or”

traits2. short generation time3. large #s of offspring4. each flower contained both male &

female organs

Mendel’s Experiments

started with true breeders cross-pollinated 2 contrasting, true-

breeding pea varieties (hybridization) true-breeding parents = P generation their hybrid offspring = F1 generation F1 self-pollinated = F2 generation

Mendel’s Experiment

did quantitative analysis of thousands of genetic crosses

deduced 2 principles of heredity:1. Law of Segregation (monohybrids)2. Law of Independent Assortment

(dihybrids)

Law of Segregation

Alleles

alternative versions of a gene

Mendel’s Model

1. Alternative versions of genes (alleles) account for variations in inherited characters.

2. For each character, an organism inherits 2 copies of a gene, one from each parent.

3. If the 2 alleles @ a locus differ, then the dominant allele determines the organism’s appearance & the recessive allele has no noticeable effect on the organism’s appearance

Mendel’s Model continued

4. Law of Segregation: the 2 alleles for a heritable character separate during gamete formation & end up in different gametes. (correlates to 2 homologous chromosomes separating in Meiosis I)

Punnett Squares

diagramatical device for predicting the allele composition of offspring from a cros between individuals froma known genetic makeup.

P signifies dominant p signifies recessive

More Genetic Vocabulary

Homozygous: having 2 identical alleles for a given gene

Heterozygous: having 2 different alleles for a given gene

Phenotype: the observable physical & physiological traits of an organism, determined by its genetic makeup

Genotype: the genetic makeup or set of alleles of an organism

Testcross: breeding an organism of unknown genotype with a homozygous recessive to determine the unknown genotype

Phenotype versus Genotype

Testcross

Law of Independent Assortment

states basically that in a dihybrid cross each allele for the 2 characters being crossed has equal opportunity

Laws of Probability

Probabilities of all possible outcomes for an event = 1

outcome of any particular toss of a coin is unaffected by the results of any previous tosses

The Multiplication Rule used to determine the probability that 2

or more independent events will occur together in some specific combination

multiply the probability of 1 event by the probability of the 2nd event

The Addition Rule

the probability that any 1 of 2 or more mutually exclusive events will occur is calculated by adding their individual probabilities (which we calculate using the multiplication rule)

Time for Handouts

Beyond Simple Mendelian Genetics

Degrees of Dominance

Alleles can show different degrees of dominance or recessiveness in relation to each other

Mendel’s peas characters were examples of complete dominance (all or none)

Incomplete Dominance: neither allele is completely dominant or recessive

Incomplete Dominance

Snapdragons

Codominance

2 alleles affect the phenotype in separate, distinguishable ways

Type of Dominance?

Relationship between Dominance & Phenotype

When a dominant allele coexists with a recessive allele in a heterozygote, they do not actually interact.

It’s in the pathway from genotype to phenotype that dominance & recessiveness come into play

An Example

Mendel’s peas Round/wrinkled R allele codes for an enzyme that helps

convert an unbranched form of starch branched form in the seed

r codes for a defective form of same enzyme leading to an accumulation of unbranched starch which leads to excess water entering seed by osmosis

later, when seed dries it wrinkles If R present, it makes enough enzyme to

make enough branched starch to prevent wrinkling

Degree of Dominance/Recessiveness

sometimes depends on how closely we look

example: Tay Sachs disease homozygous recessive Those with it cannot metabolize certain

lipids in neurons lipids accumulate child suffers neurological events (seizures, blindness, degeneration of motor & mental performance)

Tay Sachs continued

when study heterozygotes vs. homozygous dominant individuals: heterozygotes have an intermediate level of the activity of enzyme that metabolizes this lipid than do homozygous dominant individuals

on biochemical level acts like incomplete dominance since ½ the normal enzyme activity is sufficient to prevent lipid accumulation, heterozygotes have normal phenotype

on molecular level it is really an example of codominance

Frequency of Dominant Allele

dominant allele not always more frequent allele in a population

example: polydactyly extra fingers or toes 1/400 babies born in USA some caused by presence of a dominant

allele

Multiple Alleles

most genes exist in >2 allelic forms example: ABO blood groups

Pleiotrophy

most genes have multiple phenotypic effects

Epistasis

Greek: standing apart phenotypic expression of a gene at one

locus alters that of a gene at 2nd locus example: color of labs

Polygenic Inheritance

Quantitative Characters: phenotypes vary in gradation along continuum in a population (height, skin color)

Polygenic Inheritance: an additive effect of 2 or more genes on a single phenotypic character, several genes single phenotype (converse of pleiotrophy: 1 gene several characters)

Nature /Nuture

for humans: very old ? generally, genotype is NOT associated

with a rigidly defined phenotype see range of phenotypic possibilities due

to environmental influences phenotypic range is called: norm of

reaction for a genotype generally, broadest for polygenic characters

Multifactorial Characters

The environment contributes to the quantitative nature of polygenic characters which are referred to as multifactorial influenced by genetics & environment

(nutritional status, exposure to infectious disease, general well-being)

Integrating a Mendelian View of Heredity & Variation

in place of looking at organisms as single gene single phenotype

view organism as whole: emergent properties of all genes all aspects of its phenotype

In most cases, a gene’s impact on phenotype is affected by genes & by the environment

In light of all the possibilities of gene interaction it was extremely lucky that Mendel chose to study inheritance in the garden pea he chose.

Pedigree

a diagram of a family tree with conventional symbols, showing the occurrence of heritable characters in parents & offspring over multiple generations

Pedigree Symbols

Dominant Trait

Recessive Trait

Behavior of Recessive Alleles

generally, the recessive homozygous either has a malfunctioning protein or no protein at all

heterozygous individuals produce enough of the normal protein to have “normal” phenotype & are called carriers

Behavior of Recessive Alleles

generally, genetic disorders are NOT evenly distributed among all groups of people

uneven distribution results from different genetic histories of world’s people when populations were more geographically isolated

Behavior of Recessive Alleles

when a disease-causing recessive allele is rare it is relatively unlikely that 2 carriers will meet & mate

if the 2 carriers are closely related (1st cousins) the probablity of passing on recessive traits increases (consanguinous matings)

Albinism

little or no pigment in skin, hair, eyes affects: vision, skin

Cystic Fibrosis

most common lethal genetic disease in USA

1/2500 people of European descent have CF 4% are carriers

normal allele codes for membrane protein that functions in transport of Cl-

affected individuals have defective or no Cl- membrane channel

Cystic Fibrosis

result of abnl Cl- channel: abnl high Cl- in extracellular fluid mucus

that coats certain cells to become thicker, stickier than normal

mucus more tenacious, builds up in pancreas, lungs, digestive tract, testes

has pleiotropic effects: poor digestion & absorption of nutrients (fats), chronic bronchitis, frequent bacterial infections, infertility (males), diabetes

Neurofibromatosis

autosomal recessive growths grow on

nerves skin changes (3-5%

growths cancerous) hearing loss bone damage

Sickle Cell Disease

most common inherited disorder among people of African descent

1/400 African-Americans single a.a. substituted in hgb homozygous recessive individuals: all

RBCs sickle shaped

Sickle Cell Disease

when O2 content of affected individual is low (hi altitudes, physical exertion) the sickle cell hgb molecules aggregate into rods sickle shape to RBC

sickled RBCs will clog small vessels weakness, pain, organ damage, paralysis

transfusion help prevent brain damage no cure

Sickle Cell Trait

1/10 African-Americans unusually high frequency of heterozygosity

considering homozygous recessive phenotype has such detrimental effects

Malaria parasite spends part of its life cycle in RBCs & even with only some sickeled cells present it lowers the density of the parasite reduced malarial symptoms

Dominantly Inherited Disorders

those that are lethal less common than recessive disorders

most cause death of afflicted individual all lethal alleles arise by mutations in

gametes

Achondroplasia

form of dwarfism found in heterozygotes 1/2500 people have achondroplasia

(0.01% of US) If you do not have this form of dwarfism

you are homozygous recessive for it

Huntington’s Disease

example of a lethal dominant allele that is passed on to offspring (50%) because it does not cause death until individual in mid-forties (phenotype normal til then)

degenerative, irreversible, untreatable disease of nervous system

can test DNA (tip of chromosome 4)

Huntington’s Chorea

Multifactorial Disorders

genetic (usually polygenic) + environmental components

examples: heart disease alcoholism schizophrenia bipolar disease

Genetic Testing & Counseling

use multiplication rule to determine if potential parents are carriers

each child represents an individual event it is incorrect to think: “If we have 1 child

with a recessive disease then our next 3 children will have the normal phenotype”.

Carrier Testing

available for several of the recessive disorders

law passed in 2008 forbids discrimination by insurance carriers (or employers) from dropping coverage for known carriers

Fetal Testing

Amniocentesis: amniotic fluid sample taken in 2nd trimester karyotype done on fetal cells biochemical marker assayed

Chorionic Villus Sampling: 1st trimester test by sampling placental

tissue (1 layer formed by fetus)

Fetal Testing

newest technology: test mom’s blood find fetal cells culture & test them

Ultrasound (US) can identify many anatomical abnl in fetus

Fetoscopy: scope in amniotic cavity for diagnosis, possible treatment

Intra-amniotic surgery: repair neurotube defects, heart defects…..

Newborn Screening

most hospitals screen using heel prick PKU (phenylketonuria)

recessive 1/10,000 to 1/15,000 cannot metabolize phenylalanine causes severe drop in mental capacity TX: diet free of phenylalanine