Genetics A review and also some new! Mendels Work He developed a basic understanding of genetics and inheritance. He collected data for 8 years. His sample sizes were large; he tabulated results from 28,000 pea plants. He analyzed his data with statistics (probability theory) Characteristics of Garden Peas: peas are easy to grow are inexpensive have a short generation time compared to large animals (a large number of offspring can be obtained in a short amount of time) have distinct characteristics that are easy to recognize are easily self-fertilized or cross fertilized Pea Traits Mendel concluded that the F1 plants must contain 2 discrete factors, one for each characteristic. The character that was seen in the F 1 is called dominant. The character not seen in the F 1 is called the recessive. The characteristics studied by Mendel were due to single genes. Because individuals are diploid, two letters can be used to represent the genetic make-up of an individual. In the case of seed colour, the following three gene combinations are possible: AA, Aa, and aa. Heterozygote (also called hybrid) refers to an individual that has two forms of the gene: Aa Homozygote refers to an individual that has two identical genes: AA or aa Principle of Segregation Mendels principle of segregation states that paired factors (genes) separate during gamete formation (meiosis). Because the pair of genes (AA, Aa, or aa) separate, one daughter cell will contain one gene and the other will contain the other gene. Individual (genotype)Type of gametes produced AAall gametes will contain an A Aa1/2 will contain A and 1/2 will contain a aaall a gametes Punnett Square monohybrid cross (two individuals that are heterozygous for a trait) Yy x Yy Y y Y y YY Yy yy The genetic makeup of an individual is referred to as its genotype. YY The characteristics of an individual are its phenotype. The word refers to what the individual looks like so adjectives are used. Yellow, tall etc. An individual with a recessive phenotype has two recessive genes. A dominant phenotype results from either one or two dominant genes. S s S s SS Ss ss genotype ratio: 1:2:1 ( 1 SS:2 Ss:1 ss) phenotype ratio: 3:1 ( 3 smooth: 1 wrinkled) Dihybrid CrossMendel's Dihybrid CrossesMendel's Dihybrid Crosses A dihybrid cross is two monohybrid crosses (two gene traits). Ratio of traits: 9 Brown Short tail 3 Brown long tail 3 White Short tail 1 white long tail Beyond Mendel: Other Crosses Incomplete (Partial) Dominance: Some genes are neither dominant or recessive and when mixed, blending occurs. Example: Snapdragons A - red flowers a -white flowers Aa hybrid is pink Co-dominance Two dominant alleles are expressed at the same time. Because both alleles are expressed there is no blending of traits. RR- red shorthorn cattle WW white shorthorn cattle RW roan coat ( a mixture of both red hairs and white hairs). Capital letters with superscripts are often used to represent genotypes in co-dominance. C R red coat C W white coat C R C R homozygous red C W C W homozygous white C R C W roan coat Co-dominance examples: Roan cows and Tiger striped cats RW - roan Mendel formulated 4 basic laws that are still used today: Law of Dominance Law of Unit Characters Law of Segregation Law of Independent Assortment Mendel's four laws of inheritance: 1. The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F1 generation - this trait is the dominant trait. One factor or allele masks the effect or expression of another allele. 2. The Law of Segregation: during the formation of gametes (meiosis), alleles responsible for a trait separate; and each sex cell only contains one member of the pair. This allows for recombination during fertilization. 3. The Law of Independent Assortment: alleles responsible for different traits are distributed to gametes (and thus the offspring) independently of each other. 4. Law of Unit Characters: Mendel deduced that there were units in the cell that were responsible for these traits, and that these units came in pairs. Since sexual reproduction was the mode of gene transfer, he figured that each offspring received one unit from each of the two parents. Should there be fewer recessive alleles? There is sometimes a misconception that dominant traits are more common than recessive traits. Sometimes this is true, sometimes it is not. For some traits, the dominant is more common; for other the recessive is more common. Blood type O is recessive and is the most common blood type. Huntingtons disease (nervous system) is caused by a dominant gene and the normal gene is recessive. Fortunately the dominant is uncommon. In nature, natural selection may favor one (either the dominant or the recessive) and that one will become more common over time. Other forces such as genetic drift may also cause one or the other allele to become more common. Genetic Drift in evolution Genetic drift is when chance events cause changes in frequencies of alleles in a population. Alleles are the genetic variations in a population, and they are the driving force behind the evolution of that population. The smaller the population, the greater the impact genetic drift will have. The impact is greater because there are fewer individuals, and the gene pool is smaller. If the effects of genetic drift are strong enough, the allele may be completely removed from the population, reducing the amount of variation in the population's gene pool. Examples of Genetic Drift: A wildflower population consisting of blue, purple, and pink flowers is subjected to a mudslide that kills most of the blue ones. As time progresses, blue flowers eventually die out, leaving only purple and pink wildflowers. Due to random successions of births, a town has an unusually high population of people with strawberry blonde hair, a trait that increases over time and leaves very few people with different hair colors. Genetic Drift and Colour Blindness Test Cross An individual showing a dominant trait is crossed with a recessive. If any offspring show the recessive trait, the test individual must be a hybrid. This is done by breeders because it is not possible to tell from appearance alone whether an individual showing a dominant trait is pure for the trait (homozygous) or hybrid (heterozygous). Breeders of plants and animals often need this information about their parent stock (and keep detailed breeding records). Multiple Alleles, Epistasis, Pleiotropy and Polygenetic Inheritance Pleiotropy A gene that affect more than one trait is called pleiotropy. People with Marfan syndrome may be tall, have long legs, arms and fingers, and may be near sighted. Their connective tissue is defective. If left unrepaired, it may rupture around the aorta and kill the person. All of these characteristics are due to a single gene.Marfan Flo Hyman, a 1984 silver medal Olympian in women's volleyball, was another famous athlete with Marfans. Hyman is regarded as one of the best volleyball players of all time but tragically died during a match. Her case was undiagnosed until an autopsy revealed her disorder. Other notable figures in pop culture who have Marfans include Jonathan Larson (author/composer of the musical "Rent"), Joey Ramone (of the band "The Ramones"), Robert Johnson (Blues singer & guitarist), Vincent Shiavelli (actor), and Bradford Cox (frontman of bands Deerhunter and Atlas Sound).Deerhunter EPISTASIS Alleles at one locus control the expression of alleles at another locus. This interaction is referred to as epistasis. Labrador coat colour is an example of Epistasis in that there are two genes which affect coat colour, the "E" gene, which affects the presence of a dark pigment in the coat and the "B" gene, which governs the degree to which that pigment is present in the coat, where B_ gives rise to a "black lab", but only if E_ or EE are the genotypes at the other locus. Combs in Chickens In the first decade of the twentieth century, British geneticists William Bateson and R. C. Punnett conducted research showing that the shape of the comb in chickens was caused by the interaction between two different genes. Polygenic Inheritance A polygenic trait is due to more than one gene locus. Active alleles function additively. Height (tallness) in humans is polygenic. Also: performance on IQ tests skin colour cleft palate Height (tallness) is polygenic. There are 4 loci with 2 alleles per locus (Aa, Bb,CcDd). Each active allele (upper case letter A,B,C,D) adds 3 inches of height. Males (aa,bb,cc) are 5 tall. Females (aa,bb,cc) are 47. Males (AABBCC) are 66 (6 x 3 = 18)(1ft,6 in) Females (AABBCC) are 63 Heritability Variability in polygenic traits can result from genetics and also from the environment. A measure of the relative contribution of genetics is called heritability. A trait with high heritability is determined mostly by genes. A trait with a low heritability is determined mostly by the environment. Skin pigmentation (darkness) is determined by 2 or 3 pairs of alleles, but exposure to sunlight (UV radiation) also causes the skin to darken. Genomic Imprinting Sometimes an allele is expressed differently if it is inherited from the mother than if it is inherited from the father. Huntingtons is expressed earlier if inherited from the father. Symptoms of Huntington's disease usually develop between ages 30 and 50, but they can appear as early as age 2 or as late as 80. The hallmark symptom of Huntington's disease is uncontrolled movement of the arms, legs, head, face and upper body. Huntington's disease also causes a decline in thinking and reasoning skills, including memory, concentration, judgment and ability to plan and organize. Later there is difficulty swallowing, loss of balance and mood swings. The person eventually dies, usually from pneumonia or heart failure. ABO Blood Groupssystem/v/blood-types There are four major types of human blood. There are antigens (a substance that can cause a response of the immune system) on the surface of red blood cells. 1) A antigens (type A blood) 2) B antigens (type B blood) 3) Both a and B antigens (type AB blood) 4) Neither A nor B antigens (type O blood) There are 3 alleles that control blood type: A,B and O. O Is recessive. A and B are both dominant over O but neither is dominant over the other making them co-dominant. The usual way to represent alleles in a multiple allele system is to use the capital letter I to represent a co-dominant allele and a lower case i to represent a recessive allele. A superscript letter then identifies each particular co-dominant allele. I A represents dominant allele A I B represents dominant allele B i represents recessive allele O Since there are 3 alleles, there are 6 possible genotypes: 1) I A I A 2) I A I B 3) I A i 4) I B I B 5) I B i 6) ii homo hetero hetero homo hetero homo Multiple Alleles:Human Blood Typing With human blood types, there are three alleles: A,B, or O. Referred to a multiple alleles. I is dominant to i. There are two forms of I: I A and I B but only one form of i. I A I A and I A i = blood type A I B I B and I B i = blood type B I A I B = blood type AB ii = blood type O ABO Blood Groups There are four major types of human blood. There are antigens (a substance that can cause a response of the immune system made of complex carbohydrates) on the surface of red blood cells. 1) A antigens (type A blood) 2) B antigens (type B blood) 3) Both A and B antigens (type AB blood) 4) Neither A nor B antigens (type O blood) There are 3 alleles that control blood type: A,B and O. O Is recessive. A and B are both dominant over O but neither is dominant over the other making them co-dominant. The usual way to represent alleles in a multiple allele system is to use the capital letter I to represent a co-dominant allele and a lower case i to represent a recessive allele. A superscript letter then identifies each particular co-dominant allele. I A represents dominant allele A I B represents dominant allele B i represents recessive allele O Since there are 3 alleles, there are 6 possible genotypes: 1) I A I A 2) I A I B 3) I A i 4) I B I B 5) I B i 6) ii The I A allele produces group AThe I B allele produces group B The I O allele produces group O I O is recessive to I A and I B The group A phenotype can result from genotypes I A I A or I A I O The group B phenotype can result from genotypes I B I B or I B I O The group O phenotype can result only from genotype I O I O The AB phenotype results from the genotype I A I B The alleles I A and I B are equally dominant (co-dominant) ABO blood groups How are blood types related to the six genotypes? A blood test is used to determine whether the A and/or B characteristics are present in a blood sample. It is not possible to determine the exact genotype from a blood test result of either type A or type B. If someone has blood type A, they must have at least one copy of the A allele, but they could have two copies. Their genotype is either AA or AO. Similarly, someone who is blood type B could have a genotype of either BB or BO. Blood TypePossible Genotypes AAA AO BBB BO A blood test of either type AB or type O is more informative. Someone with blood type AB must have both the A and B alleles. The genotype must be AB. Someone with blood type O has neither the A nor the B allele. The genotype must be OO. Blood TypePossible Genotypes AB OOO Blood Transfusions Rule: Match the antigen of the donor with the antibodies of the recipient. Blood TypeCan Donate ToCan Receive From AA, ABA, O BB,ABB, O AB AB, A, B, O OO, A, B, ABO Blood TypeABABO In Anti-A Serum clumpingNo clumpingclumpingNo clumping In Anti-B Serum No clumpingclumping No clumping In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. The sex chromosomes are one pair of non-homologous chromosomes. Until now, we have only considered inheritance patterns among non-sex chromosomes, or autosomes. Sex-Linked Traits Sex-linked traits are genetic characteristics determined by genes located on sex chromosomes. These genes can be on the X chromosome or on the Y chromosome. If a gene is located on the Y chromosome, it is a Y- linked gene. These genes are only inherited by males because, in most instances, males have a genotype of (XY). Females do not have the Y sex chromosome. Genes that are found on the X chromosome are called X- linked genes. These genes can be inherited by both males and females. Since genes for a trait may have two forms or alleles, one allele is usually dominant and the other is recessive. Dominant traits mask recessive traits in that the recessive trait is not expressed in the phenotype. In X-linked recessive traits, the phenotype is expressed in males because they only contain one X chromosome. The phenotype may be masked in females if the second X chromosome contains a normal gene for that same trait. An example of this can be seen in hemophilia. Hemophilia is a blood disorder in which certain blood clotting factors are not produced. This results in excessive bleeding that can damage organs and tissues. Hemophilia is an X-linked recessive trait caused by a gene mutation. It is more often seen in men than women. If a son inherits an X chromosome with the hemophilia gene, the trait will be expressed and he will have the disorder. If a daughter inherits the mutated X chromosome, her normal X chromosome will compensate for the abnormal chromosome and the disease will not be expressed. Carrier- a person or animal that transmits a disease to others without itself contracting the disease Examples of Sex-linked Traits: Red-green colorblindness Male Pattern Baldness Hemophilia Duchenne Muscular Dystrophy Importance of genetics Understanding hereditary diseases and to develop new treatmentsUnderstanding hereditary diseases and to develop new treatments Donor matchesDonor matches PaternityPaternity ForensicsForensics EvolutionEvolution Genetic Testing Would you want to know? Ethical concerns Cost Insurance companies see GATTACAGATTACA If the genotypes of the parents are known, it is possible to calculate the probability of their having an affected child (i.e. one with the defect) For example if a male achondroplastic dwarf marries a normal woman, what are their chances of having an affected child? The fathers genotype must be Dd. ( DD is not viable) The mother must be dd since she is not a dwarf There is a 50% probability of their having an affected child Dd d d Dd dd What are the probabilities if both parents are affected? Genetic counselling (Genetic defects) If two normal parents have an affected child, they must both be heterozygous ( Nn ) for the recessive allele n NNNn Nn N n nn A nn parent would have cystic fibrosis A NN parent would produce only normal children Since the parents are now known to be heterozygous it can be predicted that their next child has a I in 4 chance of inheriting the disease This chance applies to all subsequent children* Cystic fibrosis (recessive) Hb = haemoglobin Hb A is the allele for normal haemoglobin Hb S is the allele for sickle cell haemoglobin A person with the genotype Hb S Hb S will suffer from sickle cell anaemia A person with the genotype Hb A Hb A is normal The genotype Hb A Hb S produces sickle cell trait because Hb A is incompletely dominant to Hb S The heterozygote Hb A Hb S has few symptoms but is a carrier for the disease Sickle cell anaemia (recessive) Red-Green Color Blindness Sex-linked trait XCXC Y XCXC XcXc X XCXC XcXc YXCXC XCXC XCXC XCXC Y XcXc XCXC Y XcXc Normal male Normal female recessive gene Possible outcomes:X C X C X C X c X C YX c Y Normal female Normal Female (carrier) Normal male Color-blind male Predicting Offspring Genetic disorders are medical conditions caused by alleles inherited from parents. These disorders are mapped on a Pedigree. A carrier is a heterozygous individual who has no apparent abnormality but can pass on an allele for a recessive inherited genetic disorder. Tracking Human Traits A pedigree is a diagram of family relationships that symbols to represent people and lines to represent genetic relationships. These diagrams make it easier to visualize relationships within families, particularly large extended families. Pedigrees are often used to determine the mode of inheritance (dominant, recessive, etc.) of genetic diseases.. In a pedigree, squares represent males and circles represent females. Horizontal lines connecting a male and female represent mating. Vertical lines extending downward from a couple represent their children. Subsequent generations are therefore written underneath the parental generations and the oldest individuals are found at the top of the pedigree. If the purpose of a pedigree is to analyze the pattern of inheritance of a particular trait, it is customary to shade in the symbol of all individuals that possess this trait. In the pedigree, the grandparents had two children, a son and a daughter. The son had the trait in question. One of his four children also had the trait. Many human traits are controlled by single genes. True for disorders, too. Cystic fibrosis, deafness, Tay Sachs. Hitchhiker thumb. Pedigrees used to predict potential disorders in children, help make a reproductive strategy. Some people may chose to not have children but adopt instead. Autosomal Dominant and Autosomal Recessive Characteristics of autosomal dominant disorders: 1. Affected children usually have an affected parent. 2. Heterozygotes are affected. Two affected parents can produce unaffected child; two unaffected parents will not have affected children. Characteristics of autosomal recessive disorders: 1. Most affected children will have normal parents since heterozygotes have a normal phenotype. 2. Two affected parents always produce an affected child. 3. Close relatives who reproduce together are more likely to have affected children. Autosomal Dominant Disorders Achondroplasia - Achondroplasia is inherited as an autosomal dominant disorder. It is diagnosed in the first years of life and affects 1 in 26,000 births; the majority of cases are sporadic. This is the classic circus dwarf with disproportionate shortness of the limbs and large head, but apparently normal trunk. Huntington's disease - Huntington's disease is a disorder passed down through families in which nerve cells in certain parts of the brain waste away, or degenerate. Marfan's syndrome - Marfan syndrome is a genetic disorder that affects the body's connective tissue - the tissue that makes up our tendons, ligaments, joints, and muscles, including the heart, blood vessels, and eyes. People with this condition are generally very tall and slim with long arms and fingers. It's quite rare - roughly 1 in 5,000 people have it. Neurofibromatosis - is a disorder characterized by the growth of noncancerous tumors called neurofibromas. They usually form on or just underneath the skin, as well as in the brain and peripheral nervous system. But they can also develop in other parts of the body, such as the eye. Autosomal Recessive Disorders Cystic fibrosis (CF) Cystic fibrosis is one of the most common inherited single gene disorders in Caucasians. About one in 2500 Caucasian babies is born with CF and about one in 25 Caucasians of northern European descent carries the gene for CF. People with CF secrete abnormal body fluids, including unusual sweat and a thick mucus which prevents the body from properly cleansing the lungs. The mucus interrupts the function of vital organs and leads to chronic infections. Classic CF also involves the pancreas and causes decreased absorption of essential nutrients. Life expectancy has improved, but, ultimately, death most often occurs from respiratory failure. Other people with variants of CF may have only lung involvement, sinusitis, or infertility. Tay Sachs Disease Tay Sachs disease is a fatal disorder in children (usually by age 5) that causes a progressive degeneration of the central nervous system. It is caused by the absence of an enzyme called hexosaminidase A (or hex A). Without hex A, a fatty substance builds up on the nerve cells in the body, particularly the brain. The process begins early in pregnancy when the baby is developing, but is not apparent until several months after the birth. To date, there is no cure for Tay Sachs. Dr. Tay and Dr. Sachs, who originally described this condition, noted that most Tay Sachs babies were usually of eastern European Jewish origin. About one in 30 persons of Ashkenazi Jewish ancestry carries the Tay Sachs gene. Sickle cell anemia (SC) Sickle cell anemia is one of the most common, inherited single gene disorders in African-Americans. About one in 600 African-American babies is born with SC, and about one in 12 African-American people carries the gene for SC. SC involves the red blood cells, or hemoglobin, and their ability to carry oxygen. Normal hemoglobin cells are smooth, round, and flexible, like the letter "O", so they can move through the vessels in our bodies easily. Sickle cell hemoglobin cells are stiff and sticky, and form into the shape of a sickle, or the letter "C" when they lose their oxygen. These sickle cells tend to cluster together and cannot easily move through the blood vessels. The cluster causes a blockage and stops the movement of healthy, normal oxygen carrying blood. This blockage is what causes the painful and damaging complications of sickle cell disease. phenylketonuria (PKU) Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. Probability Multiplication Rule: the probability of two or more independent events occurring is equal to the product of their probabilities. What is the probability of tossing a coin two times and getting heads both times? In one coin toss heads 1/2. The probability of getting heads on the second toss does not depend on the outcome of the first toss, so the multiplication rule is used. Probability = 1/2 x 1/2 = 1/4 Additive Rule: The probability of two or more mutually exclusive events occurring is equal to the sum of their probabilities. What is the probability that a student will get an A? or a B? in a class if students generally earn the following grades: A= 10% (0.10) C= 45% B= 35% (0.35) D=10% The two outcomes (getting an A or getting a B) are mutually exclusive because you can only get one or the other. The additive rule is used to determine the overall probability of getting an A or B. 10% + 35% = 45% or ( = 0.45)