Classical (Mendelian) Genetics Gregor Mendel

GENETICS The scientific study of heredity- how traits are passed down to offspring TRAIT---Specific characteristic ( blonde hair, blue eyes)

GENE A hereditary unit consisting of a sequence of DNA that occupies a specific location (LOCUS) on a chromosome and determines a particular characteristic in an organism. (Genes undergo mutation when their DNA sequence changes)

LOCUS (Loci plural) Is a location on a chromosome where a gene occurs Loci will be written as-----6p21.2 6- chromosome number P- arm 21.2- distance from centromere

Chromosome map / IDIOGRAM Detailed diagram of all the genes on a chromosome

GENOME is an organism's complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. (more than 3 billion DNA base pairs in humans)

ALLELE Alternate forms of a gene/factor. Examples: --brown eyes vs blue eyes --blonde hair vs brown hair --dimples vs no dimples

Types of alleles Dominant: An allele which is expressed (masks the other). Recessive: An allele which is present but remains unexpressed (masked)

PHENOTYPE vs GENOTYPE Genotype: combination of alleles an organism has. (Ex- BB, Bb, or bb ) Phenotype: How an organism appears. (Ex- brown hair, blonde hair )

GENOTYPES Homozygous: Both alleles for a trait are the same. (BB- homozygous dominant, bb homozygous recessive) Heterozygous: The organism's alleles for a trait are different. (Carrier of the recessive allele) Bb

GREGOR MENDEL An Austrian Monk (1822-1884) Developed these principles without ANY scientific equipment - only his mind. Tested over 29,000 pea plants by crossing various strains and observing the characteristics of their offspring.

History Principles of genetics were developed in the mid 19th century by Gregor Mendel an Austrian Monk Developed these principles without ANY scientific equipment - only his mind. Experimented with pea plants, by crossing various strains and observing the characteristics of their offspring. Studied the following characteristics: Pea color (Green, yellow) Pea shape (round, wrinkled) Flower color (purple, white) Plant height (tall, short) MONOHYBRID CROSS- cross fertilizing two organisms that differ in only one trait SELF-CROSS- allowing the organism to self fertilize (pure cross)

GREGOR MENDEL Studied the following characteristics: 1. Pea color (Green, yellow) 2. Pea shape (round, wrinkled) 3. Flower color (purple, white) 4. Pod shape ( inflated, constricted) 5. Pod color (green, yellow) 6. Plant height (tall, short) 7. Flower position (axial, terminal)

MENDEL’S CROSSES Started with pure plants ( P1) Then made a hybrid of two pure traits P1 X P1 Made the following observations (example given is pea shape) When he crossed a round pea and wrinkled pea, the offspring (F1 gen.) always had round peas. When he crossed these F1 plants, however, he would get offspring which produced round and wrinkled peas in a 3:1 ratio.

Mendel’s Experiments Mendel noticed that some plants always produced offspring that had a form of a trait exactly like the parent plant. He called these plants “purebred” plants. For instance, purebred short plants always produced short offspring and purebred tall plants always produced tall offspring. Mendel called these the P 1 generation. (pure bred, parental) X Short Offspring Purebred Short Parents X Purebred Tall Parents Tall Offspring

Mendel’s First Experiment Mendel crossed purebred plants with opposite forms of a trait. He called these plants the parental generation , or P generation. For instance, purebred tall plants were crossed with purebred short plants. X Parent Short P generation Offspring Tall F1 generation Parent Tall P generation Mendel observed that all of the offspring grew to be tall plants. None resembled the short short parent. He called this generation of offspring the first filial , or F1 generation, (The word filial means “son” in Latin.)

Mendel’s Second Experiment Mendel then crossed two of the offspring tall plants produced from his first experiment. Offspring Parent Plants X Tall F1 generation 3⁄4 Tall & 1⁄4 Short F2 generation Mendel called this second generation of plants the second filial, F2, generation. To his surprise, Mendel observed that this generation had a mix of tall and short plants. This occurred even though none of the F1 parents were short.

TERMS TO KNOW MONOHYBRID CROSS- cross using only one trait SELF CROSS- (SELF FERTILIZATION)- produce offspring asexually P1 GENERATION-- parents- usually pure bred F1 GENERATION- 1st set of offspring (1st family) F 2 GENERATION- 2nd set of offspring (2nd family)

Laws of Inheretance Law of Segregation: When gametes (sperm egg etc…) are formed each gamete will receive one allele or the other. Law of independent assortment: Two or more alleles will separate independently of each other when gametes are formed

Developed 3 laws LAW OF DOMINANCE- one allele always shows over the other LAW OF INDEPENDENT ASSORTMENT- states that each pair of genes (chromosomes) separate independently of each other in the production of sex cells. (example– you could have brown hair and blue eyes) LAW OF SEGREGATION-

Mendel’s Law of Segregation Mendel’s first law, the Law of Segregation, has three parts. From his experiments, Mendel concluded that: 1. Plant traits are handed down through “hereditary factors” in the sperm and egg. 2. Because offspring obtain hereditary factors from both parents, each plant must contain two factors for every trait. 3. The factors in a pair segregate (separate) during the formation of sex cells, and each sperm or egg receives only one member of the pair.

Punnett Squares Genetic problems can be easily solved using a tool called a punnett square. Tool for calculating genetic probabilities A punnett square

Monohybrid cross (cross with only 1 trait) Problem: Using this is a several step process, look at the following example Tallness (T) is dominant over shortness (t) in pea plants. A Homozygous tall plant (TT) is crossed with a short plant (tt). What is the genotypic makeup of the offspring? The phenotypic makeup ?

Punnet process Determine alleles of each parent, these are given as TT, and tt respectively. Take each possible allele of each parent, separate them, and place each allele either along the top, or along the side of the punnett square.

Punnett process continued Lastly, write the letter for each allele across each column or down each row. The resultant mix is the genotype for the offspring. In this case, each offspring has a Tt (heterozygous tall) genotype, and simply a "Tall" phenotype.

Punnett process continued Lets take this a step further and cross these F1 offspring (Tt) to see what genotypes and phenotypes we get. Since each parent can contribute a T and a t to the offspring, the punnett square should look like this….

Punnett process continued Here we have some more interesting results: First we now have 3 genotypes (TT, Tt, & tt) in a 1:2:1 genotypic ratio. We now have 2 different phenotypes (Tall & short) in a 3:1 Phenotypic ratio. This is the common outcome from such crosses.

Dihybrid crosses Dihybrid crosses are made when phenotypes and genotypes composed of 2 independent alleles are analyzed. Process is very similar to monohybrid crosses. Example: 2 traits are being analyzed Plant height (Tt) with tall being dominant to short, Flower color (Ww) with Purple flowers being dominant to white.

Dihybrid cross example The cross with a pure-breeding (homozygous) Tall,Purple plant with a pure-breeding Short, white plant should look like this. F1 generation

Dihybrid cross example continued Take the offspring and cross them since they are donating alleles for 2 traits, each parent in the f1 generation can give 4 possible combination of alleles. TW, Tw, tW, or tw. The cross should look like this. (The mathematical “foil” method can often be used here) F2 Generation

Dihybrid cross example continued Note that there is a 9:3:3:1 phenotypic ratio. 9/16 showing both dominant traits, 3/16 & 3/16 showing one of the recessive traits, and 1/16 showing both recessive traits. Also note that this also indicates that these alleles are separating independently of each other. This is evidence of Mendel's Law of independent assortment

PROBABILITY Definition- Likelihood that a specific event will occur Probability = number of times an event happens number of opportunities for event to happen

What if you don’t know the GENOTYPE? Perform a TEST CROSS- cross with a homozygous recessive individual If no recessive traits appear than unknown individual was HOMOZYGOUS DOMINANT

TEST CROSS If the unknown individual was heterozygous than 50% of the offspring should have the recessive phenotype.

INCOMPLETE DOMINANCE When neither allele is completely recessive Example RR ---- red roses rr---------- white roses Rr-------pink roses In the HETEROZYGOUS individual both alleles are still visible – but not fully visible

Other Factors: Incomplete Dominance Some alleles for a gene are not completely dominant over the others. This results in partially masked phenotypes which are intermediate to the two extremes.

Other Factors: Continuous Variation Many traits may have a wide range of continuous values. Eg. Human height can vary considerably. There are not just "tall" or "short" humans

CODOMINANCE When the HETEROZYGOUS INDIVIDUAL fully shows both alleles. Example is blood type Blood Type A is dominant Blood Type B is dominant Blood Type O is recessive to both A and B Blood Type AB- is heterozygous for A and B

Multiple Alleles ABO Blood typing Phenotypes are controlled by more than 2 variances for a trait ABO Blood typing Humans have multiple types of surface antigens on RBC's The nature of these surface proteins determines a person's Blood Type. There are 3 alleles which determine blood type IA, IB, or IO. This is referred to as having multiple alleles Human blood types are designated as A, B or O. Type A denotes having the A surface antigen, and is denoted by IA Type B denotes having the B surface antigen, and is denoted by IB Type O denotes having neither A or B surface antigen, and is denoted by IO There are several blood type combinations possible A B AB (Universal recipient) O (Universal donor)

Punnett Square for blood typing AB BO O AO OO

Blood & Immunity A person can receive blood only when the donor's blood type does not contain any surface antigen the recipient does not. This is because the recipient has antibodies which will attack any foreign surface protein. Thus, Type AB can accept any blood types because it will not attack A or B surface antigens. However, a type AB person could only donate blood to another AB person. They are known as Universal Recipients. Also, Type O persons are Universal donors because they have NO surface antigens that recipients' immune systems can attack. Type O persons can ONLY receive blood from other type O persons. There is another blood type factor known as Rh. People are either Rh+ or Rh- based on a basic dominant/recessive mechanism. Not usually a problem except with pregnancy. It is possible that an Rh- mother can carry an Rh+ fetus and develop antibodies which will attack & destroy the fetal blood This usually occurs with 2nd or 3rd pregnancies, and is detectable and treatable.

Other Factors Gene interaction: Environmental effects: Many biological pathways are governed by multiple enzymes, involving multiple steps.(Examples the presence of a HORMONE) If any one of these steps are altered. The end product of the pathway may be disrupted. Environmental effects: Sometimes genes will not be fully expressed owing to external factors. Example: Human height may not be fully expressed if individuals experience poor nutrition.

Chapter 12--Sex Linkage All chromosomes are homologous except on sex chromosomes. Sex chromosomes are either X or Y. If an organism is XX, it is a female, if XY it is male. If a recessive allele exists on the X chromosome. It will not have a corresponding allele on the Y chromosome, and will therefore always be expressed

PEDIGREE ANALYSIS is an important tool for studying inherited diseases uses family trees and information about affected individuals to: figure out the genetic basis of a disease or trait from its inheritance pattern predict the risk of disease in future offspring in a family (genetic counseling)

How to read pedigrees Basic patterns of inheritance 1. autosomal, recessive 2. autosomal, dominant 3. X-linked, recessive 4. X-linked, dominant (very rare)

How to read a pedigree

Sample pedigree - cystic fibrosis female male affected individuals

Autosomal dominant pedigrees 1. The child of an affected parent has a 50% chance of inheriting the parent's mutated allele and thus being affected with the disorder. 2. A mutation can be transmitted by either the mother or the father. 3. All children, regardless of gender, have an equal chance of inheriting the mutation. 4. Trait does not skip generations

Autosomal dominant traits There are few autosomal dominant human diseases (why?), but some rare traits have this inheritance pattern ex. achondroplasia (a sketelal disorder causing dwarfism)

AUTOSOMAL RECESSIVE 1. An individual will be a "carrier" if they posses one mutated allele and one normal gene copy. 2. All children of an affected individual will be carriers of the disorder. 3. A mutation can be transmitted by either the mother or the father. 4. All children, regardless of gender, have an equal chance of inheriting mutations. 5. Tends to skip generations

Autosomal recessive diseases in humans Most common ones Cystic fibrosis Sickle cell anemia Phenylketonuria (PKU) Tay-Sachs disease

Autosomal Recessive

X-Linked Dominant 1. A male or female child of an affected mother has a 50% chance of inheriting the mutation and thus being affected with the disorder. 2. All female children of an affected father will be affected (daughters possess their fathers' X-chromosome). 3. No male children of an affected father will be affected (sons do not inherit their fathers' X-chromosome).

X-LINKED Recessive 1. Females possessing one X-linked recessive mutation are carriers 2. All males possessing an X-linked recessive mutation will be affected (why?) 3. All offspring of a carrier female have a 50% chance of inheriting the mutation. 4. All female children of an affected father will be carriers (why?) 5. No male children of an affected father will be affected

Sex linkage example Recessive gene for white eye color located on the Xw chromosome of Drosophila. All Males which receive this gene during fertilization (50%) will express this. If a female receives the Xw chromosome. It will usually not be expressed since she carries an X chromosome with the normal gene

Human Sex Linkage Hemophilia: Disorder of the blood where clotting does not occur properly due to a faulty protein. Occurs on the X chromosome, and is recessive. Thus a vast majority of those affected are males. First known person known to carry the disorder was Queen Victoria of England. Thus all those affected are related to European royalty.

LINKAGE GROUPS (pg 222) Definition- genes that are located on the same chromosome. Discovered by Thomas Hunt Morgan. Made a dihybrid cross with heterozygous fruit flies ( Gray body and Long wings) GgLl x GgLl = predicted a 9:3:3:1 ratio What ratio did he get?

Answer He only got two combinations. Gray body with long wings - DOMINANT white body with short wings- RECESSIVE And they were in a 3:1 ratio just like a standard MONOHYBRID cross. Conclusion– these GENES must be on the same chromosome.

Further studies of Morgan Wanted to find out which traits were linked together on the same chromosome. Linked many traits together (remember that fruit flies have only 4 chromosomes)

During his many linkage studies found some mutations While working with the gray body and long wing linkage. Occasionally he had some flies come out Gray body with short wings and White body with long wings How could this be?

CROSSING OVER- forms new genetic combinations Long wings White body Gray body Short wings Long wings White body Short wings Gray body

CHROMOSOME MAPPING New question- where are the genes located on a chromosome? How far apart are the genes on a chromosome?

Using the rate of CROSSING OVER to determine location.

CHROMOSOME MAPPING The PERCENTAGE of crossing over is equal to ONE MAP UNIT on a chromosome.