Overview: Drawing from the Deck of genes

Ch 14: Mendel and the Gene Idea What genetic principle account for the passing of traits from parent to offspring? -the blending hypothesis is the idea the genetic material for 2 parents blend together -the particulate hypothesis is the idea that parents pass on discrete heritable units (genes) -this hypothesis can explain the reappearance of traits after several generations Mendel documented a particulate mechanism through his experiments with garden peas Concept 14.1: Mendel used the scientific approach to identify two laws of inheritance 14.2: the law of probability govern mendelian inheritance 14.3: inheritance patterns are often more complex than predicted by simple mendelian genetics 14.4: many human traits follow mendelian patterns of inheritance Mendel discovered basic principle of heredity by breeding garden peas in carefully planned experiments Advantages of pea plants for genetic study -there are many varieties with distinct heritable features, or characters (such as flower color); character variants ( such as purple of white flowers) are called traits -why peas? o Each flower has sperm-producing organ (stamens) & egg producing organ (carpel) o Cross-pollination (fertilization between diff plants) involves dusting pollen to plant Advantages of pea plants for genetic study: -character -traits -mating of plants can be controlled -each pea plants: sperm-producing organs (stamens) and egg-producing organ (carpets) -cross-pollination (fertilization b/w diff plants) can achieve by dusting pollen to other Mendel chose to track only characters that occurred in two distinct alternative forms He also used variety that were true-breeding (plants that produce offspring of the variety when they self-pollinate) In typical experiment, Mendel mated 2 contrasting, true-breeding varieties, a process called hybridization - the true-breeding parents are the P generation - the hybrid offspring of the P generation are called F1 generation - when F1 individuals self-pollinate or cross-pollinate with other F1 hybrids, the F2 generation is produced When Mendel crossed contrasting, true-breeding while the purple flowered pea plants, all of he F1 hybrids were purple Crossing of F1 hybrids had lots of the F2 plants had purple flowers, but some had white Mendel discovered a ration of about 3:1, purple to white flowers, in F2 generation Reasoned that only the purple flower factor was affecting flower color in the F1 hybrid Mendel called purple color dominant trait and the white flower a recessive trait Mendel observed same pattern of inheritance in six other pea plant characters, each representation by two trait What Mendel called a heritable factor is what we now called a gene Mendel developed hypothesis to explain 3:1 inheritance pattern observed in F2 offspring The four related concepts make up this model Concepts can be related to what now is known about genes and chromosomes

Key concepts

C 14.1: Mendel used the scientific approach to identify two laws of inheritance

Mendels experimental, quantitative approach

The law of segregation

Memdels model

 First: alternative version of genes account for variations in inherited characters For Ex: gene for flower color in pea plants exists in two versions (purple and white)-these alternative versions of a gene are now called alleles Each gene resides at a specific locus on a specific chromosome Second: for each character, an organism inherits two alleles, one from each parent Mendel made this deduction w/o knowing about the role of chromosomes Two alleles at a particular locus may be identical, as in the true-breeding plants of Mendels P generation Alternatively, the two alleles at a locus may differ, as in the F1 hybrids Third: if the two alleles at a locus differ, then one (dominant allele) determines the organisms appearance, and other (recessive) has no noticeable effect on appearance In flower-color ex, F1 plants had purple flowers bcc the allele for that trait is dominant Fourth (now known as law of segregation): two alleles for a heritable character separate (segregate) during gamete formation and end up in diff. gametes -thus, an egg or a sperm gets only one of 2 alleles that are present in organism Segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis Mendels segregation model accounts for the 3:1 ratio observed in numerous crosses Possible combinations of sperm and egg can be shown using a Punnett square Capital letter represents dominant allele, and lowercase letter represent a recessive allele Useful genetic vocabulary Organism with 2 identical alleles for a character is said to be homozygous (true breeding) Organism that has 2 diff alleles for a gene is said to be heterozygous (not true breeding) Bcc of diff effect of dominant and recessive alleles, an organisms traits dont always reveal its genetic composition. Therefore, we distinguish - phenotype, or physical appearance - genotype, or genetic makeup How can we tell the genotype of an individual with the dominant phenotype? could be either homozygous dominant or heterozygous Answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individual: ? X rr If any offspring display recessive phenotype, mystery parent must be heterozygous Mendel derived the law of segregation by following a single character the two alleles for a heritable character separate (segregate) during gametes formation and end up in different gametes F1 offspring produced in this cross were monohybrids, individuals that are heterozygous for one character A cross b/w such heterozygote is called a monohybrid cross Mendel identified his second law of inheritance (the law of independent assortment) by following two characters at the same time Crossing two true-breeding parents differing in two characters produced dihybrids in the F1 generation, heterozygous for both characters A dihybrid cross, a cross b/w F1 dihybrids, can determine whether two characters are transmitted to offspring as a package of independently Using dihybrid cross, Mendel developed the law of independent assortment Law of independent assortment states each pair of alleles during gamete formation but this law applies only to genes on different, non-homologous chromosomes or hose

The testcross

Law of Segregation

Law of independent assortment

far apart on the same chromosome Genes located near each other on the same chromosome tend to be inherited together C 14.2: The law of probability govern Mendelian inheritance Mendels laws of segregation and independent assortment reflect the rules of probability As in coin toss, outcome of one toss has no impact on the outcome of the next toss In the same way, alleles of one gene segregate into gametes independently of another genes alleles Multiplication rule states that the probability that two o more independent events will occur together is the product of heir individual probabilities Probability in an F1 monohybrid cross can be determined using the multiplication rule Segregation in heterozygous plant is like flipping a coin. Each gamete has chance of carrying the dominant allele and a chance of carrying the recessive allele Addition rule states that the probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities Rule of addition can be used to figure out the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous We can apply the x and + rules to predict the outcome of crosses involving multiple characters Dihybrid or other multi-character cross is equivalent to two or more independent monohybrid crosses occurring simultaneously In calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied Many heritable characters are not determined by only one gene with two alleles However, the basic principles of segregation and independent assortment apply even more complex pattern of inheritance

The multiplication rule applied to monohybrid crosses

The addition rule applied to monohybrid crosses

Solving complex genetic problems with the rule of probability

C 14.3: Inherietance patterns are often more complex than predicted by simple Mendelian genetics Extending mendelian genetics for a single gene

Inheritance of characters by a single gene may deviate from a simple mendelian patterns in the following situations: -when alleles are not completely dominant or recessive -when a gene has more than two alleles -when a gene produces multiple phenotypes Complete dominance occurs when phenotypes of heterozygote and dominant homozygote are identical Incomplete dominance, phenotype of F1 hybrids is somewhere between the phenotypes of two parental varieties Codominance, two dominant alleles affect phenotype in separate, distinguishable ways A dominant allele does not subdue a recessive allele; alleles dont interact that way Alleles are simply variations in a genes nucleotide sequence For any character, dominance/recessive relationships of alleles depend on the level at which we examine the phenotype Dominant alleles are not necessarily more common in populations than recessive allele 1/400 babies in US is born with extra finger or toes Dominant allele for this unusual trait is dominant for the more common trait of 5 fingers

Degrees of dominance

Incomplete dominance

Frequency of dominant alleles

Co-dominance & multiple alleles

Most genes exist in populations in more than two allelic forms -blood groups four phenotypes of the ABO blood group in humans determine by three alleles for the enzyme (I) that attaches carbohydrates to red blood cell outer membrane The enzyme encoded by the -IA allele adds the A carbohydrate; IB adds B carb; i adds neither Most genes have multiple phenotypic effects, a property called pleiotropy For Ex: pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as cystic fibrosis and sickle- cell disease Multiple genes- one trait is affected by many genes Epistasis, one gene alters the phenotypic expression of a second gene Labrador retrieves (&many other mammals) coat color depends on two genes One gene determines the pigment color Other gene determines whether pigment will be deposited in the hair Quantitative characters are those that vary in the population along a continuum and usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotype, e.g. skin color in humans Phenotype for a character depend on environment & genotype called multifactorial traits The norm of reaction is phenotypic range of a genotype influenced by the environment

Pleiotropy- one gene many effects

Polygenic inheritance

Nature and Nurture: the environmental impact on phenotype Integrating a menelian view of heredity and variation C 14.4: many human traits follow mendelian patterns of inheritance

An organisms phenotype includes its physical appearance, internal anatomy, physiology, and behavior Organisms phenotype reflects its overall genotype and unique environmental history Human are not good subjects or genetic research - generation time is too long - parents produce relatively few offspring - breeding experiments are unacceptable However, basic mendelian genetic endures as the foundation of human genetic A pedigree is a family tree that describes the interrelationships of parents and children across generations allowing particular traits to be traced and future probability determined Many genetic disorders (mild to life-threatening) are inherited in a recessive manner and are only in homozygous individuals Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with recessive disorders are born to go carries parents Albinism is a recessive condition characterized by a lack of pigmentation in skin & hair If a recessive allele that caused a disease is rare, then the chance of two carriers meeting and mating is low - consanguineous mating (incest) increases chanve of mating between tow carriers Most societies and culture have laws or taboos against marriages between close relatives Cystic fibrosis is the most common lethal genetic disease in the US, striking one out of every 2500 people of European descent - defective or absent chlorine transport channel is plasma membranes leading to build up of chlorine ions outside the cell

Recessively inherited disorder

Cystic fibrosis (recessive)

 Symptoms include mucus buildup in some internal organs and abnormal absorption in nutrients in the small intestine Sickle-Cell disease (recessive): a genetic disorder with evolutionary implications Sickle-cell disease affects one our of 400 African Americans -cause by substitution of a single amino acid in hemoglobin protein in red blood cell In homozygous individuals, all hemoblin is abnormal (sickle-cell) resulting in physical weakness, pain, organ damage, and even paralysis, but.. Heterozygous (said to have sickle cell trait) are usually healthy but may suffer some symptoms (~1 in 10 africans has sickle cell trait) Heterozygous are less than susceptible to the malaria parasite, so there is an advantage to being heterozygous Few human disorders caused by dominant allele(lethal alleles are rare, arise in mutations) Achondroplasia is a rare form of dwarfism caused by a rare dominant allele in which the fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4 is mutated Timing of onset of a disease significantly affects its inheritance Huntingtons disease is a degenerative disease of the nervous system -the disease has no obvious phenotypic effect until individual is around 35 to 40 -once the deterioration of nervous system begins the condition is irreversible and fatal Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and environmental components Little is understood about the genetic contribution to most multifactorial diseases Genetic counselors can provide information to prospective parents concerned about a family history for a specific disease Counseling based on mendelian genetics and probability rule -used family histories, genetic counselors help couples determine the odds that their children will have genetic disorders Tests for identifying carriers - for growing number of diseases, tests are available that identify carriers and help define the odds more accurately An aminocentesis, the liquid that bathes the fetus is removed and tested In chorionic villus sampling (CVS), a sample of placenta is removed and tested Other techniques, such as ultrasound and fetoscopy, allow fetal health to be assessed visually in utero Some genetic disorders can be detected at birth by simple tests that are now routinely performed in the US 1.Define the following terms: true breeding, hybridization, monohybrid cross, P generation, F1 generation, F2 generation 2.Distinguish between the following pairs of terms: dominant and recessive; heterozygous and homozygous; genotype and phenotype 3.Use a Punnett square to predict the results of a cross and to state the phenotypic and genotypic ratios of the F2 generation 4.Explain how phenotypic expression in the heterozygote differs with complete dominance, incomplete dominance, and codominance 5.Define and give examples of pleiotropy and epistasis 6.Explain why lethal dominant genes are much rarer than lethal recessive genes

Dominantly inherited disorder

Huntingtons disease: a late-onset lethal disease

Multifactorial disorders

Genetic testing and counseling

Fetal testing

New born screening

You should now be able to

7.Explain how carrier recognition, fetal testing, and newborn screening can be used in genetic screening and counseling (RrTt x RrTt) phenotypic ratio 9:3:3:1 in offspring = both parents are heterozygous for both genes (RrTt x rrtt) makes a ration of 1:1:1:1, made bt recessive genotype and individual heterozygous for both traits Epistasis- one gene alters another

Polygenic inheritance two or more genes effect a single phenotype