Patterns of Inheritance Chapter 9 Patterns of Inheritance

Purebred or mixed breed – who’s the best pet? Purebreds and mutts – why the difference?

Chapter 9: Patterns of Inheritance Purebreds and Mutts-A Difference of Heredity Genetics - the science of heredity A similar genetic background offspring have similar physical and behavioral traits Purebred dogs show less variation than mutts True-breeding individuals are useful in genetic research (mice, microbes, plants) Behavioral characteristics are also influenced by environment

Early Genetics Studies 9.1 The science of genetics has ancient roots Early attempts to explain heredity have been rejected by later science Hippocrates' theory of Pangenesis Particles from each part of the body travel to eggs or sperm and are passed on Early 19th-century biologists' “blending” hypothesis Traits from both parents mix in the offspring

Gregor Mendel – the Father of Genetics 9.2 Experimental genetics began in an abbey garden, 1860’s Gregor Mendel crossed pea plants that differed in certain characteristics Started with true-breeding varieties Controlled matings Traced traits from generation to generation

Mendel’s Findings 1. Traits were inherited in predictable patterns 2. Different forms of factors control inherited traits “factors” = genes

Parts of a flower Female – carpel (pistil) - stigma - style LE 9-2b Female – carpel (pistil) - stigma - style - ovary, with ovules Petal Male – stamen - anther with pollen - filament Stamen Carpel Parts of a flower

Manually cross-pollinate LE 9-2c Removed stamens from purple flower White Carpel Parents (P) Purple Transferred pollen from stamens of white flower to carpel of purple Stamens Pollinated carpel matured into pod Planted seeds from pod Offspring (F1) MENDEL Manually cross-pollinate Let seeds mature Planted seeds; observed offspring

Mendel’s contrasting traits in peas LE 9-2d Flower color Purple White Mendel’s contrasting traits in peas Flower position Axial Terminal Seed color Yellow Green Seed shape Round Wrinkled Pod shape Inflated Constricted Pod color Green Yellow Stem length Tall Dwarf

Terminology of Mendelian genetics Pure, or True-breeding: offspring are identical, from self-fertilizing parent Hybrid: offspring are a mix of two different parents Self-fertilization: eggs are fertilized by pollen of same flower (pollen carries sperm) Cross-fertilization (cross): fertilization of eggs by pollen from a different plant

Parent generation: Traits and genes of parents in a cross (P) Contrasting traits: different varieties of the same trait, easily distinguished (ex. tall and short) Factors: term Mendel used to describe the unit of inheritance. We know “factors” are “genes” Parent generation: Traits and genes of parents in a cross (P) Filial generations: offspring (F1- offspring of P) (F2 – offspring of F1)

Which trait appears? Law of Dominance For each characteristic, an organism inherits two alleles, one from each parent Homozygous: two alleles are identical Heterozygous: two alleles are different The Law of Dominance: If the two alleles of an inherited pair differ, the dominant allele determines the organism's appearance The recessive allele has no noticeable effect on the organism's appearance

Phenotype and Genotype Alleles in gametes form new combinations in the zygote An organism's appearance does not always reveal its genetic composition Phenotype: Expressed (physical) traits Genotype: Genetic makeup, alleles Example: tall = TT or Tt short = tt

purple flower X white flower LE 9-3a P generation (true-breeding parents) Purple flowers White flowers All plants have purple flowers F1 generation F2 generation Fertilization among F1 plants (F1  F1) of plants have purple flowers have white flowers  Purple = P White = p purple flower X white flower F1 – all purple F2 –1/4 white 3 4 1 4

Law of Dominance Green seeds X yellow seeds: Green trait disappears in F1 - Is not lost or altered (hidden by yellow) Law of Dominance - only the dominant trait appears when different alleles are present The reappearance of the recessive trait in ¼ F2 suggests that genes come in pairs which separate when gametes form

Mendel’s Law of Segregation 9.3 Mendel's law of segregation describes the inheritance of a single characteristic There are alternative forms (alleles) of genes that account for variation in inherited characteristics The Law of Segregation: A sperm or egg carries only one allele for each inherited trait, because allele pairs separate from each other during gamete production

Law of Segregation Genes are in pairs Separate when gametes form Gametes unite randomly in fertilization  Form new gene combinations Law of Segregation Allele pairs separate in meiosis and go into different gametes, but make new pairs when they combine in the zygote

Genetic makeup (alleles) LE 9-3b P plants Gametes Genetic makeup (alleles) All Pp F1 plants (hybrids) F2 plants Sperm Phenotypic ratio 3 purple : 1 white PP pp All P All p Eggs Genotypic ratio 1 PP : 2 Pp : 1 pp P p Pp Phenotype = physical trait Genotype = alleles that make that trait 1 2 1 2 Ratios: expected offspring of each type

LE 9-4 Gene loci Dominant allele P a B P a b Recessive allele Genotype: PP aa Bb Homozygous for the dominant allele Homozygous for the recessive allele Heterozygous 9.4 Homologous chromosomes carry genes for the same traits at the same loci

Segregation and Recombination A Punnett Square is a Handy Way of Analyzing Crosses Punnett square is a handy way to analyze a cross In a Punnett square for a monohybrid cross, the Principle of Segregation is applied. Segregation and Recombination

Law of Independent Assortment 9.5 Each pair of alleles separates independently of other allele pairs during gamete formation Dihybrid cross Mate true-breeding parents who differ in two characteristics The F1 generation exhibits only the dominant phenotypes The F2 generation exhibits a phenotypic ratio of 9:3:3:1

Are different traits inherited together? Are Different Characters Like Color and Shape Inherited Together or Inherited Independently? Are different traits inherited together? True-breeding parents F1 – all have dominant phenotypes F2 – recombination yields four different phenotypes Mendel performed dihybrid crosses to find out. Mendel’s conclusion: Different characters are inherited independently.

(alternative arrangements) Fertilization among the F1 plants LE 9-18 Independent Assortment - Random alignment in metaphase I All round yellow seeds (RrYy) F1 generation R y r Y R r r R Metaphase I of meiosis (alternative arrangements) Y y Y y R r r R Anaphase I of meiosis Y y Y y R r r R Metaphase II of meiosis Y y Y y Y y Y y Y Y y y Gametes R R r r r r R R 1 4 RY 1 4 ry 1 4 rY 1 4 Ry Fertilization among the F1 plants F2 generation 9 :3 :3 :1 (See Figure 9.5A)

contradict hypothesis LE 9-5a Independent Assortment Hypothesis: Dependent assortment Hypothesis: Independent assortment P generation RRYY rryy rryy RRYY rryy Gametes RY ry Gametes RY  ry F1 generation RrYy RrYy Sperm Sperm 1 4 RY 1 4 rY 1 4 Ry 1 4 ry 1 2 RY 1 2 ry 1 4 RY 1 2 RY RRYY RrYY RRYy RrYy F2 generation Eggs 1 4 rY 1 2 ry RrYY rrYY RrYy rrYy Eggs Yellow round 1 4 Ry 9 16 RRYy RrYy RRyy Rryy 3 16 Green round Actual results contradict hypothesis 1 4 ry Yellow wrinkled RrYy rrYy Rryy rryy 3 16 Actual results support hypothesis 1 16 Green wrinkled 9 dom/dom : 3 dom/rec : 3 rec/dom : 1 rec/rec

Mendel’s round and wrinkled seeds The Reality of “Round and Wrinkled” – Two Alternative Traits of the Seed Shape Character Mendel’s round and wrinkled seeds Note that each of seed is a new individual of a different generation – seeds are not of the same generation as the plant that bears them.

Genes for coat color and vision sort independently LE 9-5b Genes for coat color and vision sort independently Blind Blind Phenotypes Genotypes Black coat, normal vision B_N_ Black coat, blind (PRA) B_nn Chocolate coat, normal vision bbN_ Chocolate coat, blind (PRA) bbnn Mating of heterozygotes (black, normal vision) BbNn  BbNn Phenotypic ratio of offspring 9 black coat, normal vision 3 black coat, blind (PRA) 3 chocolate coat, normal vision 1 chocolate coat, blind (PRA)

9.6 Geneticists use the test cross to determine unknown genotypes Mate an individual of unknown genotype with a homozygous recessive individual Each of the two possible genotypes (homozygous or heterozygous) gives a different phenotypic ratio in the F1 generation ANY recessive offspring  both parents gave recessive allele

Testcross: Black – could be BB or Bb Genotypes LE 9-6 Black – could be BB or Bb Testcross:  Genotypes B_ bb Two possibilities for the black dog: BB or Bb Gametes B B b b Bb b Bb bb Offspring All black 1 black : 1 chocolate

Probability 9.7 Mendel's laws reflect the rules of probability Events that follow probability rules are independent events One such event does not influence the outcome of a later such event

Use Probability to Solve Genetics Problems The rule of multiplication: The probability of two events occurring together is the product of the separate probabilities of the independent events ex. - chance of something happening? 1/2 - chance of two things happening at the same time? 1/2 x 1/2

Heads or tails = ½ Two heads at once = ½ x ½ LE 9-7 F1 genotypes Bb male Heads or tails = ½ Two heads at once = ½ x ½ Formation of sperm Bb female Formation of eggs 1 2 1 2 B b B B B b 1 2 B 1 4 1 4 F2 genotypes 1 2 b B b b b 1 4 1 4

Multiplication rule in genetics Chance of one gamete with B = 1/2 Chance of other gamete with B = 1/2 Chance of BB in zygote = ½ x ½ = ¼

Rule of Addition The rule of addition: The probability for an event which can occur in two or more alternative ways is the sum of the separate probabilities of the different ways B b 1/4 1/2

Addition rule in genetics Hybrid can be Bb or bB 1/4 + 1/4 = 1/2

Using probability to predict outcome Probability that an allele will go into a gamete: If genotype is AA  probability that gamete will have A = 1 If genotype is Aa  probability that gamete will have A = ½ probability that gamete will have a = ½

Probability of getting hybrid from Bb x Bb Cross Bb x Bb, probabilities in F1: to get BB = ½ B x ½ B = ¼ to get Bb = ½ B x ½ b = ¼ OR ½ b x ½ B = ¼ then ¼ + ¼ = ½

VARIATIONS ON MENDEL'S LAWS 9.11 The relationship of genotype to phenotype is rarely simple Mendel's principles are valid for all sexually reproducing species However, many characteristics are inherited in ways that follow more complex patterns

Variations on Mendel - Incomplete Dominance 9.12 Incomplete dominance results in intermediate phenotypes Complete dominance Dominant allele has same phenotypic effect whether present in one or two copies Incomplete dominance Heterozygote exhibits characteristics intermediate between both homozygous conditions

LE 9-12a P generation Red RR White rr  Gametes R r F1 generation Pink Rr Allele for red and allele for white – neither is dominant over the other pink hybrids 1 2 1 2 Gametes R r Sperm 1 2 1 2 R r 1 2 Red RR Pink rR R F2 generation Eggs 1 2 Pink Rr White rr r

Blue Andalusian Chicken Black (BB) X White (WW)  “Blue” (BW)

Hypercholesterolemia – normal gene is incompletely dominant LE 9-12b Hypercholesterolemia – normal gene is incompletely dominant Genotypes: hh Homozygous for inability to make LDL receptors HH Homozygous for ability to make LDL receptors Hh Heterozygous LDL Phenotypes: LDL receptor Cell Normal Mild disease Severe disease

Codominance – Both Alleles Are Dominant Neither allele is recessive - no blending; both phenotypes show up Roan horse has red hairs and white hairs

Codominance: Roan horse color in heterozygote Black X white  blue roan Red X white  strawberry roan

Calico Cat Calico (tortoise shell) cat has red patches and black patches, along with white

9.13 Some genes have more than two alleles in the population Multiple Alleles 9.13 Some genes have more than two alleles in the population Multiple alleles may exist for a single characteristic Example: human ABO blood group Involves three alleles of a single gene A and B alleles are codominant to each other (both alleles are expressed in heterozygotes) O allele is recessive to A and B

The ABO blood group A and B alleles are codominant (IA IB or A B) the allele for type O blood (i or O) is recessive Type A blood – genotypes AA or Ai Type B blood – genotypes BB or Bi Type AB blood - genotype AB Type O blood – genotype ii

What does “blood type” mean? ABO blood groups: Identification proteins on red blood cell membrane Rh + or Rh – is a different protein (and different gene)

Why does blood type matter? ABO Blood Type Incompatability LE 9-13 Why does blood type matter? ABO Blood Type Incompatability Blood Group (Phenotype) Antibodies Present in Blood Reaction When Blood from Groups Below Is Mixed with Antibodies from Groups at Left Genotypes O A B AB Anti-A Anti-B O ii IAIA or IAi A Anti-B IBIB or IBi B Anti-A AB IAIB

Polygenic inheritance Two or more genes control a single trait Example: human skin color, height, eye color Skin color - three genes

Fraction of population LE 9-15 P generation  aabbcc (very light) AABBCC (very dark) Polygenic traits show a range of phenotypes F1 generation  AaBbCc AaBbCc 1 64 6 64 15 64 20 64 15 64 6 64 1 64 Sperm 1 8 1 8 1 8 1 8 1 8 1 8 1 8 1 8 20 64 F2 generation 1 8 1 8 15 64 1 8 1 8 Fraction of population Eggs 1 8 6 64 1 8 1 8 1 64 1 8 Skin color

Coat color in labs - interaction of two genes Black (B) is dominant over brown (b) B makes more melanin pigment than b Yellow (E) is dominant over (e) E allows B to be fully expressed; ee blocks B BB, Bb = black EE,Ee = B gene not blocked bb = chocolate ee = B gene blocked (yellow)

9.16 The Environment affects many traits Environment can influence expression of a gene Examples: a) Skin darkens when exposed to sun b) plants lacking soil nutrients or water will not grow well

Environment can affect a genetic trait Colder body parts have darker fur

THE CHROMOSOMAL BASIS OF INHERITANCE 9.18 Chromosome behavior accounts for Mendel's laws Chromosome theory of inheritance Walter Sutton, 1902, observed meiosis – chromosomes follow Mendel’s laws Chromosomes are in pairs Chromosome pairs separate independently of other pairs during meiosis Genes occupy specific loci on chromosomes Thus, chromosome behavior during meiosis and fertilization accounts for inheritance patterns

Thomas Hunt Morgan Thomas Hunt Morgan performed some of the most important studies of genetics and crossing over in the early 1900s Morgan in the fly room

T. H. Morgan and fruit fly genetics Used the fruit fly Drosophila melanogaster Determined that crossing over was the mechanism that "breaks linkages" between genes Found that genes could be located on specific chromosomes

SEX CHROMOSOMES AND SEX-LINKED GENES Chromosomes determine sex in many species Humans: X-Y system Male is XY; the Y chromosome has genes for the development of testes Female is XX; absence of a Y chromosome allows ovaries to develop

Dad determines gender of baby (male) (female) 44 + XY 44 + XX Dad determines gender of baby - gamete has Y  boy - gamete has X  girl Mom always gives X Parents’ diploid cells 22 + X 22 + Y 22 + X Sperm Egg 44 + XX 44 + XY Offspring (diploid)

Sex Chromosomes carry some non-gender genes X chromosome holds many more genes than does the Y chromosome

Sex-linked genes have a unique inheritance pattern Most sex-linked genes in humans are on the X chromosome Males only get one X, so recessive trait shows in them more often Females need two recessive alleles for trait to show Example: eye color in fruit flies

Eye color in fruit flies is sex-linked “Wild” type (normal) is red; “Mutant” is white

LE 9-23b Female Male XRXR  Xr Y Sperm Xr Y Eggs XR XRXr XRY R = red-eye allele r = white-eye allele

LE 9-23c Female Male XRXr  XRY Sperm XR Y XR XRXR XRY Eggs Xr XrXR

LE 9-23d Female Male XRXr  Xr Y Sperm Xr Y XR XRXr XRY Eggs Xr Xr Xr

Sex-linked disorders in humans Color- blindness – cannot tell some colors - red/green most common 2) Hemophilia – blood does not clot Duchenne muscular dystrophy – muscles waste away ALD -Lorenzo

Can you see a number?

Green Color-Blind A: 70, B: --, C: 5, D: 2 Test Yourself With The Table Below Numbers That You Should See If You Are In One Of The Following Four Categories: [Some Letter Choices Show No Visible Numbers]  Normal Color Vision  A: 29,  B: 45,  C: --,  D: 26  Red-Green Color-Blind  A: 70,  B: --,  C: 5,  D: --  Red Color-blind  A: 70,  B: --,  C: 5,  D: 6  Green Color-Blind  A: 70,  B: --,  C: 5,  D: 2

CONNECTION - Pedigrees 9.8 Genetic traits in humans can be tracked through family pedigrees The inheritance of many human traits follows Mendel's laws The dominant phenotype results from either the heterozygous or homozygous genotype The recessive phenotype results from only the homozygous genotype Family pedigrees can be used to determine individual genotypes

Some human traits are controlled by single genes

Dd Joshua Lambert Dd Abigail Linnell D ? John Eddy D ? Hepzibah LE 9-8b Dd Joshua Lambert Dd Abigail Linnell D ? John Eddy D ? Hepzibah Daggett D ? Abigail Lambert dd Jonathan Lambert Dd Elizabeth Eddy Dd Dd dd Dd Dd Dd dd Female Male Deaf Hearing

9.19 Genes on the same chromosome tend to be inherited together Gene Linkage 9.19 Genes on the same chromosome tend to be inherited together Punnett and Bateson Linked genes Lie close together on the same chromosome Usually inherited together Generally do not follow Mendel's law of independent assortment

Not accounted for: purple round and red long Experiment Purple flower PpLl  PpLl Long pollen Observed offspring Prediction (9:3:3:1) Phenotypes Sometimes linked genes do NOT stay together. Why? Purple long Purple round Red long Red round 284 21 55 215 71 24 Explanation: linked genes Parental diploid cell PpLl P L p l Meiosis Most gametes P L p l Fertilization Sperm P L p l P L P L P L Most offspring P L p l Eggs p l p l p l P L p l 3 purple long : 1 red round Not accounted for: purple round and red long

Mapping genes on a chromosome 9.21 Geneticists use crossover data to map genes on a chromosome Morgan and his students greatly advanced understanding of genetics Alfred Sturtevant used crossover data to map genes in Drosophila Recombination frequencies map the relative positions of genes on chromosomes

9.20 Crossing over produces new combinations of alleles During meiosis, homologous chromosomes undergo crossing over Trade pieces of crossed chromosomes Produces new linkage groups  new combinations of alleles in gametes Percentage of recombinant offspring is called the recombination frequency

LE 9-20a A B a b A B a b A b a B Tetrad Crossing over Gametes

LE 9-20c Experiment Gray body, long wings (wild type) Black body, vestigial wings  GgLl ggll Female Male Offspring Gray long Black vestigial Gray vestigial Black long The farther apart are two genes on a chromosome, the more often they cross over. 965 944 206 185 Parental phenotypes Recombinant phenotypes Recombination frequency = 391 recombinants 2,300 total offspring = 0.17 or 17% Explanation G L g l GgLl (female) ggll (male) g l g l G L g l G l g L g l Eggs Sperm G L g l G l g L g l g l g l g l Offspring

LE 9-21b Chromosome g c l 17% 9% 9.5% Recombination frequencies

Mutant phenotypes Wild-type phenotypes LE 9-21c Mutant phenotypes Short aristae Black body (g) Cinnabar eyes (c) Vestigial wings (l) Brown eyes Long aristae (appendages on head) Gray body (G) Red eyes (C) Normal wings (L) Red eyes Wild-type phenotypes

Hybrid Vigor - Heterozygotes are often healthier - mule (horse X donkey): bigger and stronger than donkey or horse - liger (lion X tiger): bigger than both

Sickle Cell Allele as advantage heterozygotes are more resistant to malaria

Polyploidy – multiple sets of chromosomes Stops cell division  diploid gametes - in animals – don’t survive - common in plants  increases hardiness, size of flowers, fruits, crop yields

Lethal alleles Cause death in homozygotes - ex. some human genetic disorders - Achondroplasia - Manx cat

Pleiotropy - A single gene can have many effects 9.14 A single gene may affect many phenotypic characteristics Example: sickle cell disease Allele causes abnormal hemoglobin Affects blood flow to all body organs Many severe physical effects Heterozygotes are usually healthy

- Many effects from a single gene Individual homozygous for sickle-cell allele Pleiotropy - Many effects from a single gene Sickle-cell (abnormal) hemoglobin Abnormal hemoglobin crystallizes, causing red blood cells to become sickle-shaped Sickle-cells 5,555 Clumping of cells and clogging of small blood vessels Breakdown of red blood cells Accumulation of sickled cells in spleen Physical weakness Heart failure Pain and fever Brain damage Damage to other organs Spleen damage Anemia Impaired mental function Pneumonia and other infections Kidney failure Paralysis Rheumatism

CONNECTION – Gene Disorders 9.9 Many inherited disorders in humans are controlled by a single gene Thousands of human genetic disorders follow simple Mendelian patterns of inheritance Recessive disorders Most genetic disorders Can be carried unnoticed by heterozygotes Range in severity from mild (albinism) to severe (cystic fibrosis) More likely to occur with inbreeding

 Parents Offspring Normal Normal Dd Dd Sperm D d Dd Normal (carrier) LE 9-9a  Parents Normal Dd Normal Dd Sperm D d Dd Normal (carrier) DD Normal D Offspring Eggs Dd Normal (carrier) d dd Deaf

Some Genetic Disorders

Cystic Fibrosis The most common inherited disorder in Americans of European descent - thick mucus, clogs small ducts in body - harms lungs, digestive, and other systems - one in 2000 are carriers - treatment – physically clear mucus from lung, drugs to thin mucus, no cure

PKU - phenylketonuria Defective enzyme cannot break down phenylalanine, an amino acid (one in 10,000) Brain degeneration – early death Treated with diet (no foods with phenylalanine)

Sickle cell disease Red blood cells shrink into crescent shape Block tiny blood vessels  many organs damaged More common among people of African descent 1 in 400 (heterozygote – increased resistance to malaria

Sickle cell disorder

Tay- Sachs Disease More common among Jews from eastern Europe 1 in 3500 Lack an enzyme to break down a lipid Brain degeneration, early death

Disorders caused by dominant genes Dominant disorders Some serious but not lethal ex. achondroplasia – a form of dwarfism 1 in 25,000

Huntington’s Disease Caused by a dominant allele (one in 25,000) Brain degeneration  death Does not appear until mid-life

9.10 New technologies can provide insight into one's genetic legacy Gene and Fetal testing 9.10 New technologies can provide insight into one's genetic legacy Family history? Pedigrees can give probability Blood tests for some genes Helps couples decide about having children Find carriers of many genetic disorders

Routine Fetal and Newborn Tests Fetal imaging Ultrasound imaging uses sound waves to make a picture of the fetus Newborn screening Some genetic disorders can be detected at birth by routine blood or urine tests Video: Ultrasound of Human Fetus 1

Amniocentesis Get sample of cells before baby is born Amnion: membrane sac surrounding baby Watery amniotic fluid has baby skin cells in it 15-18 weeks

CVS – Chorionic Villus Sampling Chorion - tissue in early placenta Placenta - organ which brings baby oxygen and nutrients, removes wastes - made of both mother and baby cells 10-11 weeks

Amniocentesis Chorionic Villus Sampling LE 9-10a Amniocentesis Chorionic Villus Sampling Amniocentesis Chorionic villus sampling (CVS) Ultrasound monitor Needle inserted through abdomen to extract amniotic fluid Suction tube inserted through cervix to extract tissue from chorionic villi Ultrasound monitor Fetus Fetus Placenta Placenta Chorionic villi Uterus Cervix Cervix Uterus Amniotic fluid Centrifugation Fetal cells Fetal cells Biochemical tests Several weeks Several hours Karyotyping

What??!! Is this for real?