Chapter 9 - Patterns of Inheritance I. Genetics – the science of heredity

A. Selective breeding

1. pitbull/rottweiler vs. daschund

2. dogs from wolves – 14000 years ago

a) border collie – selected for by herders to control flocks of animals

b) Labrador retriever – selected by hunters, good at retrieving wounded prey – less aggressive – don’t want dogs to eat the kill!

B. Genetics and the Environment – an intimate collaboration

1. friendly rottweiler

2. shyness in humans has a genetic component – can be amplified or reduced by environment.

a) ex. Tom Hanks 3. [READ] Avshalom Caspi and Terrie Moffitt [interview with Moffitt here on npr] made quite a splash in 2002 when they published the paper “Role of Genotype in the Cycle of Violence in Maltreated Children” in Science. They reported that maltreated children would differ in the development of antisocial personality and violent behaviour depending upon whether or not their genotype conferred high or low levels of MAOA expression, a neurotransmitter-metabolizing enzyme. Thus, Caspi and Moffitt showed that a genetic variation may moderate the influence of environmental factors on behaviour in a rather dramatic manner, fueling the growing suspicion that the old nature/nurture dichotomy is much too simplistic. Behaviour is most probably not determined by either an innate genetic Bauplan or the ever changing forces of our surroundings. In Caspi and Moffitt’s study, at least, children with a low-level MAOA genotype only developed an antisocial personality if maltreated (if you happen not to be maltreated, a low-level MAOA polymorphism will not cause you to develop an antisocial personality); but, at the same time, maltreatment doesn’t affect children with a high- level MAOA polymorphism, so the maltreatment is not a cause in itself either. Genes and environmental factors interact to produce behaviour, and the real question is how they do so.

C. What we will exam in this chapter

1. rules that govern how inherited characteristics are passed from parent to offspring 2. how to predict the ratio of offspring with particular traits

3. how the behavior of chromosomes during gamete formation (meiosis) and fertilization accounts for the patterns of inheritance we observe. II. History

A. Pangenesis - Hippocrates – ancient Greece 400BC

1. Pangenesis – particles (pangenes) travel from each part of the organism’s body to the gametes, changes that occur in the body during life are passed as well (work out and get big muscles, you pass the muscles on…lol)

a) long been falsified, somatic cells have zero influence over gametes

2. this idea of passing traits acquired over ones lifetime persisted into the early 19th century!!

B. Blending hypothesis – early 19th century biologists used ornamental plants

1. established that offspring inherit traits from both parents

2. hereditary materials mix like mixing blue and yellow paints to make green.

a) ex. pure black lab breeds with pure chocolate lab, offspring will be somewhere b/w black and chocolate and you can never get the original colors.

b) Falsified – what happens is you get all black and if you mate the black, you get some black, but brown can return! Mendel’s Principles III.Experimental genetics began in an abbey garden A. Modern genetics began in the 1860’s (1856-63) with an Augustinian monk by the name of Gregor Mendel.

B. Mendel was university trained in experimental technique! – he was a physics teacher!

C. 3 keys to Mendel’s Success

1. Choice of organism:

a) He studied peas for their advantages:

(1) They grow easily and were readily available in many varieties

(2) Have short life cycles (1 year) – annual plant

2. Experimental approach:

a) If you want to do hereditary experiments you need to be able to control mating (you need to know who the parents are). So how did Mendel control this?

b) Self fertilization vs. cross fertilization in plants

(1) Self-fertilization – sperm carrying pollen released from stamens land on the tip of the egg containing carpel of the same flower – naturally done by pea plants (pedals enclose stamen and carpel)

(a) He controlled self-fertilization by simply covering flower with a small bag.

(2) Cross-fertilization – fertilization of one plant by pollen from a different plant.

(a) He prevented self-fertilization by cutting off the stamens of immature flowers

(b) Dusted this female plant with pollen from another plant

(c) Carpel will develop into a pod, containing seeds

(d) He planted these seeds and allowed them to grow 3. Selection of characteristics to study

a) Seven characteristics, each of which has two distinct forms.

b) Each characteristic was defined by a single gene – he didn’t know this, he was lucky

c) If you want to understand how something works, you don’t’ pick the most complicated form like a Ferrari. You pick the simplest form like a lawn mower engine to learn the basic principles first. D. Mendel needed a starting point. He needed true breeding plants.

1. True breeds – plants that when self fertilized produced offspring identical to the parent in the desired trait.

a) Ex. if you self fertilized a plant with yellow peas, all the offspring would have yellow peas all the time.

E. Now Mendel was ready to ask what would happen if he crossed the different varieties? (ex. Crossed purple flower plants with white flower plants)

1. Hybrids – the offspring of two different varieties (offspring of the purple-white flower cross)

2. Cross-fertilization = Cross or hybridization

3. P generation – the parental plants (P for parental)

4. F1 generation – the hybrid offspring of the P generation (F for filial – Latin for “son”).

5. F2 generation – (filial 2) offspring of self-fertilization or crossing of F1 generation.

F. Published his work in 1866 arguing for discrete, heritable factors (genes) that retain their individuality when transmitted from generation to generation. IV. Mendel’s principle of segregation describes the inheritance of a single characteristic (AIM: How can the inheritance of a single characteristic be described?)

A. Monohybrid cross – parents differ in only one characteristics (purple flower x white flower with all other characteristics the same).

1. Results – Out of 929 F2 offspring, 705 (~3/4) were purple and 224 (~1/4) were white.

2. The same was observed for all seven characteristics 3. There is no blending! Heritable factors (today called genes) retain their individuality generation after generation.

B. Four hypothesis were developed by Mendel:

1. There are alternative forms of genes called alleles

2. An organism has 2 genes for each inherited characteristic, one from each parent – They may be the same allele or different alleles

3. A sperm or egg carries only one allele for each inherited trait, because allele pairs separate (segregate) from each other during the production of gametes

4. When the two genes of a pair are different alleles and one is fully expressed while the other has no noticeable effect on the organism’s appearance, the alleles are called the DOMINANT allele and the RECESSIVE allele, respectively

a) Uppercase letters represent dominant alleles

b) Lowercase letters represent recessive alleles

c) Conventions for alleles: P, the dominant (purple) allele, and p, the recessive (white) allele. P generation: PPx pp; their gametes P and p; F1 generation – All Pp P Plants PP X pp   Gametes All P All p  F1 plants All Pp (hybrids)   Gametes ½ P ½ p    Phenotypic ratio  3:1 F2 Plants *Punnet Square of PP X pp Genotypic ration  1:2:1 d) Gentoype = genetic makeup

(1) Homozygous dominant - PP

(2) Homozygous recessive - pp

(3) Heterozygous - Pp e) Phenotypes – what we see in the organism – physical appearance – ex. purple flower or white flower

f) Punnet Square – used to keep track of the gametes (sides of the square) and offspring (cells within the square) – shows possible combinations of gametes.

C. How can the disappearance of a trait in one generation, then reappear the following generation be explained?

a) PRINCIPLE of SEGREGRATION  pairs of genes segregate (separate) during gamete formation; the fusion of gametes at fertilization pairs genes once again V. Homologous chromosomes bare the two alleles for each characteristic

A. Alleles – alternative forms of genes – reside at the same locus (location; loci is plural) on homologous chromosomes VI. The principle of independent assortment is revealed by tracking two characteristics at once

A. Dihybrid cross – the mating of parents differing in two characteristics

B. Question: Are traits passed as a package or independently? Do white flowers always go with yellow peas? – Go over experiment

1. Breed two strains true – ex. RRYY (round yellow) and rryy (wrinkled green)

2. Hybridize the two strains resulting in F1: RrYy

3. Allow F1 to self-fertilize a) Four possible gametes: RY, Ry, rY, ry if not linked 42 = 16 genotypic possibilities, only two if linked RY and ry 22 = 4 genotypic possibilities. So what is observed?

4. Results:

a) F1 exhibits only dominant phenotype (expected)

b) F2 has a phenotype ratio of 9:3:3:1 (round yellow: round green: wrinkled yellow: wrinkled green)

c) Use Punnett square to analyze results

5. Conclusion – Independent Assortment (most often)

C. Principle of independent assortment – each pair of alleles segregates independently during gamete formation.

VII. Geneticists use the testcross to determine unknown genotypes

A. test cross – crossing an unknown genotype (expressing the dominant phenotype – is it homo- or heterzygous) with the recessive phenotype.

1. If homozygous dominant – phenotype ratio in F1 is all dominant

2. If heterozygous – F1 phenotype ratio is half dominant and half recessive VIII. Mendel’s principles reflect the rules of probability

A. Mendel had a strong background in Math

B. Probability scale ranges from 0 to 1

1. 0 representing the chance an event will NOT occur

2. 1 presenting that an event WILL occur

3. All probabilities must add up to 1 a) Ex. flip a coin – chance of heads is .5, and chance of tails is .5 = 1

b) Drawing card. Chance of drawing an Ace of spades? Chance of drawing any other card?

C. Independent events – an event that does not influence the outcome of a later event

1. coin flipping

a) 1st flip does not influence 2nd – still ½ chance of getting heads.

D. Flip a coin twice (compound event). What is the probability of getting heads both times?

1. Rule of multiplication – probability of 2 events occurring together is the product of the probabilities of the 2 events occurring apart

2. Toss two coins at the same time – chance of getting two heads is ½ * ½ , same as if they were separated by time.

3. Getting a kina of hearts and then a queen of spades? 1/52 x 1/52

E. Rule of multiplication in genetics

1. Bb x Bb

2. What is the probability of getting a bb genotype?

a) What is probability of getting sperm with b gene?

b) What is probability of getting egg with b gene?

c) Multiply the two independent events and you get ¼

F. Rule of addition - the probability that an event can occur in two or more ways is the sum of the probability of each event 1. probability of getting a jack of hearts or a queen of spades? 1/52 + 1/52

2. What is the probability of getting a Bb genotype?

a) Probability of getting a Bb is ¼ and probability of getting a bB is ¼. Probability of getting either is ¼ + ¼ = ½.

G. Applying these rules allows us to predict probabilities for very complex crosses (like trihybrid) that would require too complex a Punnet Square

1. Trihybrid cross

a) AaBbCc x AaBbCc

b) What is the probability of getting aabbcc

(1) Look at them each independently

(2) odd of getting aa = ¼, bb = ¼, cc = ¼ and ¼ x ¼ x ¼ = 1/64 c) We could also make a 64-section Punnett square

2. Example 1:

a) Probability of a recessive phenotype occurring in a monohybrid cross (PP x pp) is ¼.

b) The probability of two recessives occurring together in a dihybrid cross (RRYY x rryy and getting rryy) is ¼ * ¼ = 1/16.

c) What about a trihybrid? ¼ * ¼ * ¼ = 1/64. IX. Genetic traits in humans can be tracked through family pedigrees

A. Mendel’s principles apply to many human traits

1. Fig. 9.8A shows some simple dominant-recessive traits at one gene locus

2. A dominant trait does NOT mean that it is normal or more common than a recessive one.

a) wild-type traits (trait prevailing in nature) are not always dominant traits.

b) recessive is often more common than dominant

B. How do we know how particular human traits are inherited?

1. We can’t cross humans like peas and dogs! Can’t control mating.

2. Must analyze the results of natural mating

a) collect family history of trait

b) assemble info into a family tree or pedigree (a visual family history of a trait).

(1) squares are male and circles are female (2) colored symbols indicate an affected individual

C. Carriers – people with one copy of the allele for a recessive disorder, symptomless

X. Many inherited disorders in humans are controlled by a single gene

A. >1000 known human genetic disorders inherited as dominant or recessive traits controlled by a single gene locus

1. Recessive disorders

a) cystic fibrosis

(1) autosomal recessive – must have two copies of recessive allele

(2) carried by 1 in 25 Caucasians

(3) 1 in 1800 Caucasians affected

(4) excessive secretion of thick mucus from lungs, pancreas and other organs (a) interferes with breathing, digestion, liver function and renders person vulnerable to pneumonia and other infections.

(5) untreated, most die by 5 years old

(6) diet, antibiotics, frequent pounding of chest and back to clear lungs can prolong life to adulthood.

b) Taboos or laws forbidding marriages b/w close relatives

2. dominant disorders

a) achondroplasia

(1) 1 in 25,000

(2) homozygous dominant causes death of the embryo

(3) Thus 99.99% of population are homozygous recessive

b) What about lethal dominant alleles? Would you expect them to be common?

c) Huntington’s disease

(1) a lethal dominant that escapes elimination – does not cause death until beyond reproductive age.

(2) causes uncontrollable movements in all parts of body, brain cell loss leading to loss of memory and judgement…depression. Loss of motor skills prevents swallowing and speaking. XI. Fetal testing can spot many inherited disorders early in pregnancy

A. Amniocentesis – extract ~10ml of amniotic fluid from preganant woman between 14 and 20 weeks (fetus is 6 inches long)

1. the fluid part is immediately tested for certain telltale chemicals

2. the cells are cultured, allowing them to undergo cell division to a sufficient number to do

a) biochemical tests like DNA testing or appearance of specfic proteins, etc…

b) karyotyping (need cell division)

3. 1% complication rate (maternal bleeding, miscarriage, premature birth)

B. Chronic villus sampling (CVS) – narrow tube inserted through vagina and cervix used to suction off a small amount of fetal tissue (chorionic villi) from the placenta –

1. cells are undergoing rapid cell divisiosn – perfect for karyotyping

2. advantages over amnio

a) done earlier - 10-12 weeks

b) fast, only takes a few hours to get results

3. can’t test for everything an amnio tests for

4. 2% complication rate

C. Ultrasound imaging – use sound waves to look for anatomical deformities.

1. can be used in combo with CVS or amnio to determine position of fetus and where to insert needle. D. Maternal blood tests

1. help identify fetuses at risk for further testing like amnio.

2. look for alpha-fetoprotein (AFP) – protein produced by fetus

a) high levels may indicate Down syndrome or neural tube defects

3. Triple screen test

a) measures AFP, estriol, and human chorionic gonadotropin (hCG) - hormones produced by placenta

b) abnormal levels also point towards Down syndrome

E. Summary – family history, blood tests, genetic counseling and fetal testing Variations on Mendel’s Principles XII. The relationship of genotype to phenotype is rarely simple

A. Mendel’s principles work for some traits, but most are inherited in ways that follow more complex patterns – these complex patterns are extensions of Mendel’s rules, not exceptions. XIII. Incomplete dominance results in intermediate phenotypes

A. Incomplete dominance – F1 hybrids have a phenotype in between that of the parental varieties

B. One allele is not completely dominant over the other XIV. Many genes have more than two alleles in the population A. Example : ABO blood groups in humans

B. Individuals have only two alleles per trait, but there are three possibilities here.

C. These alleles code for the presence of two different carbohydrates (A or B) or no carbohydrate (O) on the surface of RBC’s. Phenotype Genotypes O Ii A IAIA or IAi B IBIB or IBi AB IAIB D. Codominance – both alleles are expressed in heterzygotes (AB blood)

E. Relevance in transfusions

1. Type O = universal donor

2. Type AB = universal acceptor

F. Blood type can be quick tool to disprove or suggest parentage in paternity suits (DNA is MUCH better!) XV. A single gene may affect many phenotypic characteristics

A. Pleiotropy – impact of a single gene on more than one characteristic

1. Sickle cell anemia

a) (strikes 1 in 500 African American children born in US annually) –

b) 100,000 a year die from it in world

2. homozygous for sickle cell allele  results in abnormal hemoglobin  results in sickle-shaped red blood cells  breakdown of RBC’s, clogging of small blood vessels, accumulation of sickle cells in spleen, etc… (Fig. 9.14)

3. results in physical weakness, anemia, pain and fever, heartfailure, brain damage, spleen damage, damage to other organs, kidney failure, etc… XVI. Genetic testing can detect disease causing alleles

A. CARRIER TESTING  used to determine if a person carries a harmful allele

B. DIAGNOSTIC TESTING  can confirm or rule out an existing disorder C. PRENATAL TESTING  checks for disorders in unborn babies

D. NEWBORN SCREENING  can catch disorders right after birth; allowing infants to receive medical care

E. PREDICTIVE TESTING  used to determine a person’s risk for developing on specific disorder on the future XVII.A single characteristic may be influenced by many genes

A. Known as polygenetic inheritance – additive effect of two or more genes on a single phenotypic characteristic

B. Ex. Skin Color, Height The chromosomal basis of inheritance XVIII. Chromosome behavior accounts for Mendel’s principles

A. chromosome theory of inheritance – genes are on chromosomes and thus the behavior of chromosomes during meiosis and fertilization accounts for observed inheritance patterns.

B. Mendel knew NOTHING about genes and chromosomes

C. Principle of Segregation – homologous pairs of chromosomes accounts for this

D. Principle of independent assortment – accounted for by the fact that there are several sets of homologous chromosomes – Mendel’s 7 garden pea traits all separated independently because they were all on different chromosomes.

E. What if Mendel’s traits were on the same chromosome? XIX. Genes on the same chromosome tend to be inherited together

A. Linked genes – genes located on the same chromosome

B. Inheritance of these traits does not follow principles of independent assortment – they are normally inherited together

C. So how might nature unlink linked genes? XX. Crossing over produces new combinations of alleles

A. In the case of many linked genes, there are some offspring that appear to unlink the genes and follow independent assortment B. These situation are accounted for by crossing over, which recombines linked genes into assortments of alleles not found in parents

C. Recombination frequency – the percentage of offspring that are recombinants (having a genotype not found in either parent)

D. Early recombination experiments were demonstrated in fruit flies by embryologist T. H. Morgan and colleagues in the early 1900’s. XXI. Geneticists use crossover data to map genes

A. Drosophila melanogaster – the fruit fly – model organism that has greatly aided in our understanding of genetics (the modern day pea plant).

1. Many characteristics, short life cycle, easily raised and bred, only 4 chromosomes, chromosomes can easily be visualized in nondividing cells in the salivary glands.

B. A. H. Sturtevant (colleague of Morgan) developed a technique for using crossover data to map the location of genes on chromosomes on which they are linked

C. The greater distance between two genes on the same chromosome, the more likely it is that a crossover event will occur between those genes

D. Thus, one can use recombination frequency to ESTIMATE the location of genes on a chromosome relative to other genes. Chromosomes and Sex-linked genes XXII.Chromosomes determine sex in many species

A. Sex chromosomes – many animals (humans, fruit flies, others) have a pair of chromosomes that determine their gender – designated X and Y – The X-Y system

1. Eggs are all X, sperm (X or Y) determines sex

2. XY – male

3. XX – female

B. Other sex determination systems exist:

1. X-O system – grasshoppers, crickets, roaches:

a) females – XX and

b) males – XO (O = absence of sex chromosome)

(1) egg is always X, sperm can be X or O

2. Z-W system (opposite of XY system) – certain fish, butterflies, and birds –

a) males ZZ

b) females are ZW

(1) egg has either Z or W, sperm are all Z

3. Chromosome number – most ants and bees –

a) females develop from fertilized eggs

(1) and are thus diploid.

b) Males develop from non-fertilized eggs (no fathers)

(1) and are thus haploid. 4. Many plants have separate sexes – male and female flowers on different organisms

a) spinach, marijuana, and others – X-Y system

b) wild strawberries – Z-W system

C. Not all organisms have separate sexes

1. Most plant and some animal species have individuals that produce both sperm and eggs.

a) Monoecious - plants of this type (pea plants!)

b) Hermaphroditic – animals of this type – earthworms and garden snails

D. Many other exotic sex determination systems exist

1. Temperature-dependent sex determination – some species of reptiles – alligators, turtles – sex determined by temperature of the egg!! – so not ALWAYS genetic. XXIII. Sex-linked genes exhibit a unique pattern of inheritance

A. sex-linked genes – any gene found on the sex chromosomes

B. Sex chromosomes contain genes specifying sex as well as genes having nothing to do with sex.

1. Those not related to sex are most often found on which gene, X or Y? Explain… (X of course)

C. Example using fruit fly eye color

1. Red is dominant to white

2. Y chromosome does not have a locus for eye color

a) male phenotype based solely on X

b) First go over the possible combinations for male and female. c) XrY have white eyes, XRY have red XXIV. Why do sex-linked disorders affect mostly males?

A. Males only have one X-chromosome, so we only need to inherit one copy of the compromised allele gene. Females need to inherit two compromised alleles – less likely.

B. RED-GREEN COLOR BLINDNESS  a common sex- linked disorder characterized by a malfunction of light sensitive cells in the (eyes?)

1. involves several genes

a) normal vision – we see 150 colors

b) color blind – see fewer than 25

C. HEMOPHILIA  a sex-linked recessive trait characterized by excessive bleeding due to a defective gene involved in blood clotting

D. DUCHENNE MUSCULAR DYSTROPHY  a sex-linked recessive disorder characterized by a progressive weakening and loss of muscle tissue