Dominance is between genes at the same locus, ie, genes that control the same trait. An example might be the R allele being dominant over the r allele. Epistasis is between genes at different loci. An example might be the influence of the C gene over the R gene, so that the absence of a C allele makes the R allele not function...
congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life (neonatal disease), regardless of causation. Of these diseases, those characterized by structural deformities are termed "congenital anomalies"; that is a different concept (MeSH) which involves defects in or damage to a developing fetus.
MIC150 - Chap 2 Extension Of Mendelian Genetics
EXTENSION OF MENDELIANGENETICS1. Codominance2. Incomplete dominance3. Multiple alleles4. Lethal alleles5. Epistasis6. Polygenic inheritance7. Linked genes8. Crossover values and gene mapping9. Sex linked genes
INTRODUCTION• Mendelian inheritance describe – patterns that obey two laws • Law of segregation • Law of independent assortment – Includes simple Mendelian inheritance • A single gene with two different alleles • Alleles display a simple dominant/recessive relationship
INTRODUCTION (cont)• Simple Mendelian inheritance – Traits affected by a single gene – Two alleles exist for this gene – 3:1 phenotypic ratio in the F2 generation
INTRODUCTION (cont)• Dominant alleles are usually indicated either by: – an italic uppercase letter (D)• Recessive alleles are usually indicated either by: – an italic lowercase letter (d)• If no dominance exists, italic uppercase letters and superscripts are used to denote alternative alleles (R1, R2, CW, CR).
MENDELIAN INHERITANCE• Alternative forms of a gene are called alleles.• Mutation is the source of alleles.• The wild-type allele is the one that occurs most frequently in nature and is usually, but not always, dominant.
MENDELIAN INHERITANCE (cont)• Wild-type alleles (dominant) are the most prevalent alleles in a population – Encoded protein is generally • Functional • Made in the proper amount – Confer various phenotypes • e.g., Purple flowers, round seeds, etc.
MENDELIAN INHERITANCE (cont)• Mutant alleles (recessive) have been altered by mutation – Tend to be rare in natural populations – Commonly defective in ability to express functional protein • Encoded protein is often: – Produced in reduced amount (decreased synthesis) – Less functional (decreased function) – Often inherited in a recessive fashion – Confer various phenotypes • e.g., White flowers, wrinkled seeds, etc.
MENDELIAN INHERITANCE (cont)• Genetic disease are caused by mutant alleles• In many human genetic diseases, the recessive allele contains a mutation. What kind of genetic disease that you know of containing recessive alleles? (submit in two weeks time)
MENDELIAN INHERITANCE (cont)• Simple dominant/recessive relationship – Fairly common among many genes – One copy of the dominant allele is sufficient to produce the dominant phenotype • Recessive allele does not affect the phenotype of heterozygotes
• Production of functional protein is reduced by 50% – 50% is adequate to provide a normal phenotype – Homozygotes produce more wild-type protein than necessary
LETHAL ALLELES• Gene is an essential for survival – An estimated 1/3 of all genes are essential for survival• Mutant allele is a lethal allele • Has potential to cause death • Inherited in a recessive manner • Absence of a specific protein may result in a lethal phenotype
LETHAL ALLELES (cont)• Many lethal alleles prevent cell division – These will kill an organism at an early age• However, some lethal alleles exert their effect later in life – e.g. Huntington disease causes a progressive degeneration of the nervous system • Age of onset is generally 30 – 50 • Progressive degeneration of nervous system, dementia and early death
LETHAL ALLELES (cont)• Some lethal alleles exert their effect only under certain environmental conditions – “Conditional lethal alleles” – e.g., Temperature-sensitive (ts) lethals • May kill developing Drosophila larva at 30oC • Larva will survive if grown at 22oC • Why do you think this is the case? (submit in two weeks time)
LETHAL ALLELES (cont)• Two types of Lethal alleles – Dominant lethal alleles – Recessive lethal alleles
Dominant LA• The LA modify the 3:1 phenotypic ratio into 1:1• The individuals with a dominant LA die before they can produce the progeny. Therefore, the mutant dominant LA is removed from the population in the same generation in which it arose.• Huntington’s disease is caused by a dominant LA and even though it is not described as lethal, it is invariably lethal in that the victim experiences gradual neural degeneration for some years before death occurs.
Recessive LA• They maybe of two kinds (i) one which has no obvious phenotypic effect in heterozygotes and (ii) one which exhibit a distinctive phenotype when in heterozygous condition.• Recessive LA don’t cause death in the heterozygous form because a certain threshold of protein output is maintained. In the homozygous form, the protein output doesn’t meet the threshold, causing death.• Eg diseases; cystic fibrosis, Tay-Sachs disease, sickle cell anemia, and brachydactyly.
Recessive LA (cont)• One coat colour of ranch foxes is caused by recessive lethal gene. This gene causes a death if both recessive alleles are possessed by the same individual.• It occasionally arise by mutation from a normal allele.• However, in many cases lethal genes became operative at time the individual become sexually mature.• Complete lethality, thus is the case where no individual of a certain genotype attain the age of reproduction.
LETHAL ALLELES (cont)• Lethal alleles may produce ratios that seemingly deviate from Mendelian ratios – e.g., “Creeper” phenotype in chickens • Shortened wings and legs • Creeps rather than walking normally • Creeper chicken are heterozygous Creeper Cp - shortlegged, - autosomal semi-lethal incomplete dominant
All “creeper” birds are heterozygous• Creeper x Normal • Creeper x creeper 2:1 1:1 phenotypic ratio • Creeper allele is a – Creeper phenotype is recessive lethal dominant – Creeper homozygotes are dead
CODOMINANCE• Any given gene may have more than two alleles and the phenotype of both alleles are in heterozygote.• Two alleles are expressed• Do not blend the phenotype• ‘Co’ – means together• Co-dominance = both alleles are dominant – Example: different blood types and group antigens
• Also an example of multiple alleles, will be explain further later
CODOMINANCE (cont)• Different from Segregation Law• As both of the alleles are dominant, we are going to use ‘R’ for the colour of cow’s hair• RR = all red hair• RW = all white hair• RRRW = red and white hair• RR RR x RW RW = 100% RRRW
INCOMPLETE DOMINANCE• Heterozygotes sometimes display a phenotype intermediate between the homozygotes – e.g., Flower color in the four-o’clock, snapdragons, carnations, etc. – Homozygous red (CRCR) x homozygous white (CWCW) • F1 offspring (CRCW) are heterozygous and pink • F2 offspring display 1:2:1 phenotypic and genotypic ratios
1:2:1 phenotypic ratio but NOT the 3:1 ratio 50% of the CR observed as in simple protein is not Mendelian Inheritance sufficient toproduce the red phenotype
• Many traits appear to be dominant – Closer examination shows that some are actually incompletely dominant – e.g., Seed shape in Mendel’s peas • RR and Rr genotypes produce round seeds • rr genotypes produces wrinkled seeds – Decreased starch deposition
EXERCISE1. Predict the phenotype ratios of offspring when a homozygous white cow is crossed with a roan (red and white) bull.2. What is the phenotypes and genotypes for parent cattle be if a farmer wanted only cattle with red fur?3. A cross between a black cat and a tan cat produces a tabby pattern (black and tan fur together) a) What pattern of inheritance does this illustrate? b) What is the percentage of kittens will have tan fur if a tabby cat is crossed with a black cat?
MULTIPLE ALLELES• Individuals possess two copies of each gene – At most, they possess two different alleles• Means there are same/more than three alleles• The situation exclude the dominant and recessive effects• All the alleles show own effects in inheritance• Eg. Blood type and hair colour
MULTIPLE ALLELES (cont)• Coat color in rabbits is determined by alleles of the “C” gene – Four different alleles exist • C = full coat color • cch = chinchilla • ch = himalayan • c = albino – Any particular rabbit possesses only two alleles
MULTIPLE ALLELES (cont)• Dominant/recessive relationships between coat color alleles – C is dominant to cch, ch, and c – cch is recessive to C, but dominant to ch, and c – ch is recessive to C and cch, but dominant c – c is recessive to C, cch, ch C > cch > ch > c
MULTIPLE ALLELES (cont)• Four different alleles – C (full coat color) – cch (Chinchilla - partial defect in coloration) – ch (himalayan- pigmentation only in certain parts) • Temperature-sensitive conditional allele – c (albino- is a defective allele producing no protein necessary for pigment production)
• This is caused by tyrosinase; producing melanin• Eumelanin: black pigment and phaeomelanin (orange/yellow pigment)
MULTIPLE ALLELES (cont)• cchc x Cch cch c C Ccch Cc ch Cchch chc• Genotypes: – 1 Ccch :1 Cc : 1 Cchch : 1 chc• Phenotypes: – 2 Full: 1 Chinchilla: 1Himalayan
CONDITIONAL ALLELES• ch is a temperature-sensitive conditional allele – Results in pigmentation only in certain parts of the body • Encoded enzyme functions only in cooler areas of the body – Ends of extremities, tail, paws, nose, ears – Similar temperature-sensitive alleles are found in other animals • e.g., Siamese cat
MULTIPLE ALLELES (cont)• Red blood cells contain carbohydrate chains on their plasma membranes – “Antigens” • Recognized by immune system’s antibodies – A, B, and O antigens determine human blood type • Synthesized by three alleles of a single gene • IA, IB, and i
MA: RED BLOOD CELLS• What are antigens? (submit in two weeks time)
• The “i” gene produces an enzyme – Glycosyl transferase – Attaches sugar “branches” to carbohydrate “trees” present on the surface of red blood cells • i allele encodes a defective enzyme – No sugar branches are attached • IA and IB alleles encode enzymes with different substrate specificities – Different sugar “branches” are attached
MA: RED BLOOD CELLS (cont)• i is recessive to both IA and IB – ii type O blood• IA and IB are codominant – IAIB AB blood • Possesses both A and B antigens
MA: RED BLOOD CELLS (cont)• Blood typing is essential for safe blood transfusions• The donor’s blood must be an appropriate match with the recipient’s blood• Eg. If a type O individual received blood from a type A, type B or type AB blood – Antibodies in the recipient blood will react with antigens in the donated blood cells – Donated blood will agglutinate – Life threatening situation: clogging vessels
EXERCISECross a heterozygous type A with a heterozygoustype B. 1. ___IAi____ X ____IBi___ 2. ___IAIB____ X ____ii___What is the genotypes and phenotypes?
EXERCISE• A woman with type O blood and a man who is type AB are expecting a child. What are the possible blood type of the kid?• What are the possible blood type of a child who’s parents are both heterozygous for ‘B’ blood type?• Jill is blood type O. She has two brothers (who always tease her) with blood type A and B. What are the genotypes of her parents with respect to this traits?
EPISTASISDefined as:• An inheritance pattern in which the alleles of one gene mask the phenotypic effects of the alleles of another genes
EPISTASIS• Epistasis, first defined by the English geneticist, William Bateson in 1970, is the masking of the expression of a gene at one position in a chromosome, or locus, at one or more genes at other position.• Epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes.
EPISTASIS (cont)• The genes whose phenotype is expressed is said to be epistatic, while the phenotype altered or suppressed is said to be hypostatic.• Epistasis can be contrasted with dominance, which is an interaction between alleles at the same gene locus.• Epistasis is often studied in relation to Quantitative Trait Loci (QTL) and polygenic inheritance
Example: Walnut Comb• rr and pp to be epistatic to this phenotype.• rr and pp mask a walnut comb.
P1 Pea Comb X Rose Comb PPrr ppRRF1 All Walnut Combs PpRrWhen these F1 birds are crossed, allfour phenotypes are observed:F2 PR Pr pR prPR PPRR PPRr PpRR PpRrPr PPRr PPrr PpRr PprrpR PpRR PpRr ppRR ppRrpr PpRr Pprr ppRr pprr
Ratio Description Name(s) of Relationship (Used by Some Authors)9:3:3:1 Complete dominance at both gene pairs; new phenotypes result Not named because the ratio from interaction between dominant alleles, as well as from interaction between looks likeindependent assortment both homozygous recessives9:4:3 Complete dominance at both gene pairs; however, when 1 Recessive epistasis gene is homozygous recessive, it hides the phenotype of the other gene9:7 Complete dominance at both gene pairs; however, when either Duplicate recessive epistasis gene is homozygous recessive, it hides the effect of the other gene12:3:1 Complete dominance at both gene pairs; however, when one gene is dominant, it Dominant epistasis hides the phenotype of the other gene15:1 Complete dominance at both gene pairs; however, when either gene is dominant, it Duplicate dominant epistasis hides the effects of the other gene13:3 Complete dominance at both gene pairs; however, when eithergene is dominant, it Dominant and recessive epistasis hides the effects of the other gene9:6:1 Complete dominance at both gene pairs; however, when eithergene is dominant, it Duplicate interaction hides the effects of the other gene7:6:3 Complete dominance at one gene pair and partial dominance at the other; No name when homozygous recessive, the first gene is epistatic to the second gene3:6:3:4 Complete dominance at one gene pair and partial dominance at the other; No name when homozygous recessive, either gene hides the effects of the other gene; when both genes are homozygousrecessive, the second gene hides the effects of the first11:5 Complete dominance for both gene pairs only if both kinds ofdominant alleles are No name present; otherwise, the recessivephenotype appears
POLYGENIC INHERITANCE• This term is use to refer to inheritance of quantitative traits, traits which are influenced by multiple genes and not just one.• Because many traits are spread out across the continuum, rather than being divided into black and white differences, polygenic inheritance helps to explain the way in which these traits are inherited and focused.• A related concept is pleiotropy, an instance where one gene influences multiple traits (phenotypes).
• However, in the 20th century, people were well aware that most traits are too far complex to be determined by a single gene, and the idea of polygenic inheritance was born.
POLYGENIC INHERITANCE (cont)• One easily understood example of polygenic inheritance is height. People are not just short or tall; they have a variety of heights which run along a spectrum.• Furthermore, height is also influenced by environment; someone born with tall genes could become short due to malnutrition or illness, for example, while someone born with short genes could become tall through genetic therapy.
POLYGENIC INHERITANCE (cont)• Basic genetics obviously wouldnt be enough to explain the wide diversity of human heights, but polygenic inheritance shows how multiple genes in combination with a persons environment can influence someones phenotype, or physical appearance.
POLYGENIC INHERITANCE (cont)• Polygenic traits are a result of additive effects of contribution of each genes in loci and therefore they do not follow typical dominance and recessive patterns.• The second aspect of polygenic genes are, the traits are determined by environmental variations. It means that an individual can be genetically same, but can differ in their physical appearance.
POLYGENIC INHERITANCE (cont)• Phenotypes like high blood pressure (hypertension) are not the result of a single "blood pressure" gene with many alleles (a 120/80 allele, a 100/70 allele, a 170/95 allele, etc.)• The phenotype is an interaction between a persons weight (one or more obesity genes), cholesterol level (one or more genes controlling metabolism), kidney function (salt transporter genes), smoking (a tendency to addiction), and probably lots of others too. Each of the contributing genes can also have multiple alleles.
• Skin colour is another example of polygenic inheritance, as are many congenital diseases.• Because polygenic inheritance is so complex, it can be a very absorbing and frustrating field of study.• Researchers may struggle to identify all of the genes which play a role in a particular phenotype, and to identify places where such genes can go wrong.• However, once researchers do learn more about the circumstances which lead to the expression of particular traits, it can be a very rewarding experience.
DON’T GET CONFUSED!• Multiple alleles=more than two forms of the same gene in the population e.g blood type• Polygenic traits=more than one gene contributes to the phenotype
• In pleiotropy, on the other hand, one gene is responsible for multiple things.• Several congenital syndromes are examples of pleiotropy, in which a flaw in one gene causes widespread problems for a person.
• For example, sickle cell anemia is a form of pleiotropy, caused by a distinctive mutation in one gene which leads to a host of symptoms.• In addition to causing mutations, pleiotropy also occurs in perfectly normal genes, although researchers tend to use it to track and understand mutations in particular.
LINKED GENES• The dihybrid cross we previously did assumed the genes were on different pairs of chromosomes.• Now, we want to look at an example where the genes involved are on the same chromosome.
LINKED GENES (cont)• One such example is the flower colour and pollen shape experiment done by Bateson and Punnett.• In the plants that they studied, the genes for pollen shape and flower colour are located on the same chromosome (pair) as each other, thus are inherited together.
• If the parents are PPLL × ppll, the first parent will only make gametes with PL and the second with pl, which doesnt seem too different so far.• From these parents, the F1 generation would all be PpLl.
• However, when calculating what the F2 generation will be, since the genes are located on the same pair of chromosomes, then theoretically, the only possible gametes are PL and pl (not Pl or pL). PL pl PL PPLL PpLl pl PpLl ppll• The phenotype ratio for this cross is 3:1, not 9:3:3:1 as would be expected for a “normal” dihybrid cross. Because these genes are on the same chromosome pair, they are called linked genes.
SEX LINKED GENES• This is sex-linked genes, genes located on one of the sex chromosomes (X or Y) but not the other.• Since, typically the X chromosome is longer, it bears a lot of genes not found on the Y chromosome, thus most sex-linked genes are X-linked genes.
• One example of a sex-linked gene is fruit fly eye colour.• An X chromosome carrying a normal, dominant, red-eyed allele would be symbolized by a plain X, while the recessive, mutant, white-eyed allele would be symbolized by X or Xw.• A fly with genotype XX would normally be a female with red eyes, yet be a carrier for the white-eyed allele.• Because a male typically only has one X chromosome, he would normally be either XY and have normal, red eyes, or XY and have white eyes.• The only way a female with two X chromosomes could have white eyes is if she would get an X allele from both parents making her XX genotype. The cross between a female carrier and a red-eyed male would look like this: X Y X XX XY X’ XX’ X’Y
SEX LINKED GENES (cont)• Typically, X-linked traits show up more in males than females because typical XY males only have one X chromosome, so if they get the allele on their X chromosome, they show the trait.• If a typical XX female is a carrier, 50% of her sons will get that X chromosome and show the trait. In order for an XX female to exhibit one of these X-linked traits, most of which are recessive mutations, she would have to have two copies of the allele (XX), which would mean that her mother would have to be a carrier and her father have the trait so she could get one allele from each of them.
• The Punnett square would predict that ½ of their sons (¼ of their children) would be hemophiliacs and ½ of their daughters (¼ of their children) would be carriers. Their children married other royalty, and spread the gene throughout the royal families of Europe.
SEX LINKED GENES (cont)SEX LIMITED TRAIT – Affects a structure or function of the body that is present in only male or only female – E.g. Growth of beard or breastSEX INFLUENCED TRAIT – An allele that is dominant in one sex and recessive in the other – E.g. Baldness – Heterozygous male is bald, heterozygous female is not
CROSSING OVER• Even though the alleles for different genes may be linked along the same chromosome, the linkage can be altered during meiosis.• In diploid eukaryotic species, homologous chromosomes can exchange pieces with each other, a phenomenon called crossing over.• This event occurs during prophase of meiosis I.
• Chiasma is the point where chromatids become criss-crossed and the chromosome exchange segements.• New combinantion arise from crossing over resulting in recombination and passed during the gamete formation.• When meiosis is over 2 chromosome separated to become individual chromatids and produce 4 genetically different chromosome.
GENE MAPPING• Also known as chromosome mapping, to determine linear order and distance of separation among genes that are linked to each other along the same chromosome.
GENE MAPPING (cont)• Why it is useful? – Allow geneticist to understand overall complexity and genetic organization of a particular species. – The genetic map of a species portrays underlying basis for the inherited traits that an organism display. – Help in cloning process too
GENE MAPPING (cont)• Genetic map benefits: – Locate human gene that causing diseases, this information can be used to diagnose and someday treat inherited human diseases. – Predict likelihood that a couple will produce children with certain inherited diseases. – Also important in agriculture – help in improving crops/animal through selective breeding.