Early Ideas of Genetics Saw patterns of inheritance in people and domesticated plants and animals. Bizarre chimeras explained variation- not true – heredity occurs within species. Thought traits were “blended” from parents. Traits are transmitted directly- explained by a seed “gonons” (Hippocrates) or “humuculus” (Leewenhoek)
Why Peas (Pisum sativum)? Many varieties or strains of plant. These strains are true-breeding or pure – produce the same trait generation after generation. The strains can be hybridized or strains crossed (T. A. Knight, 1790s). Can be self-fertilized or cross- fertilized.
First, alternative versions of genes –Account for variations in inherited characters, which are now called alleles Figure 14.4 Allele for purple flowers Locus for flower-color gene Homologous pair of chromosome s Allele for white flowers
Gene Locus Brown Allele Blue Allele Homologous Chromosomes ACGTACACGTAC ACGGCTACGGCT
Some Terms Locus (i)- position on a chromosome where a gene is located. Alleles- alternative forms of a gene. Different genetic information for a protein. Phenotype- “form that is shown”- physical appearance of a trait. Genotype- the sum of an organism’s alleles.
Phenotype versus Genotype Figure 14.6 3 1 1 2 1 Phenotype Purple White Genotype PP (homozygous) Pp (heterozygous) Pp (heterozygous) pp (homozygous) Ratio 3:1 Ratio 1:2:1
Some Terms Dominant Allele- an allele whose expression is readily seen; affects the phenotype more. Recessive Allele-an allele whose expression is less seen; affects the phenotype less. Homozygous- organism with two identical alleles at the same locus. Heterozygous- organism with two different alleles at one locus.
Summary of Mendel’s Crosses A cross between homozygous dominant X homozygous recessive, F 1 progeny are all heterozygous, and resemble the homozygous dominant parent in phenotype. Two alternative alleles of a gene segregate randomly.
A Testcross Figure 14.7 Dominant phenotype, unknown genotype: PP or Pp? Recessive phenotype, known genotype: pp If PP, then all offspring purple: If Pp, then 1 ⁄ 2 offspring purple and 1 ⁄ 2 offspring white: p p P P Pp pp Pp P p pp APPLICATION An organism that exhibits a dominant trait, such as purple flowers in pea plants, can be either homozygous for the dominant allele or heterozygous. To determine the organism’s genotype, geneticists can perform a testcross. TECHNIQUE In a testcross, the individual with the unknown genotype is crossed with a homozygous individual expressing the recessive trait (white flowers in this example). By observing the phenotypes of the offspring resulting from this cross, we can deduce the genotype of the purple-flowered parent. RESULTS
Testcross (Backcross) How can you tell if an organism with a dominant phenotype is a Het. or Homo.? To determine whether an individual is a Het or Homo., cross the individual with a known homozygous recessive- Testcross.
Summary of Mendel’s Crosses If cross or self-fertilize the F 2 generation, the result is a 3:1 ratio. Crosses with individuals that are heterozygous at one locus-Monohybrid Cross. The two alternative alleles segregate independently from one another and are distinct- Law of Segregation.
Law of Segregation Alternative forms of a gene (alleles) are discrete and do not blend in Hets. Alleles independently assort from each other into gametes. Each gamete has an equal probability of receiving either allele.
Do different genes also segregate independently? Examine crosses which involve two genes. (Ex. seed shape and seed color). Fig. 13.16, p. 282.) Crosses with individuals heterozygous at two different loci- Dihybrid Crosses. Genes assort independently in the F 2 with a 9:3:3:1 ratio.
YYRR P Generation GametesYRyr yyrr YyRr Hypothesis of dependent assortment Hypothesis of independent assortment F 2 Generation (predicted offspring) 1⁄21⁄2 YR yr 1 ⁄ 2 1⁄21⁄2 yr YYRRYyRr yyrrYyRr 3 ⁄ 4 1 ⁄ 4 Sperm Eggs Phenotypic ratio 3:1 YR 1 ⁄ 4 Yr 1 ⁄ 4 yR 1 ⁄ 4 yr 1 ⁄ 4 9 ⁄ 16 3 ⁄ 16 1 ⁄ 16 YYRR YYRr YyRR YyRr YyrrYyRr YYrr YyRRYyRr yyRRyyRr yyrr yyRr Yyrr YyRr Phenotypic ratio 9:3:3:1 315108 101 32 Phenotypic ratio approximately 9:3:3:1 F 1 Generation Eggs YR Yr yRyr 1 ⁄ 4 Sperm RESULTS CONCLUSION The results support the hypothesis of independent assortment. The alleles for seed color and seed shape sort into gametes independently of each other. EXPERIMENT Two true-breeding pea plants— one with yellow-round seeds and the other with green- wrinkled seeds—were crossed, producing dihybrid F 1 plants. Self-pollination of the F 1 dihybrids, which are heterozygous for both characters, produced the F 2 generation. The two hypotheses predict different phenotypic ratios. Note that yellow color (Y) and round shape (R) are dominant. A dihybrid cross: –Illustrates the inheritance of two characters Produces four phenotypes in the F 2 generation Figure 14.8
Law of Independent Assortment Genes located on different chromosomes assort independently of one another- Independent Assortment.
How would separate genes located close to one another on a chromosome be inherited?
Non-Mendelian Inheritance Complex Patterns of Inheritance: How Genes Interact
Incomplete Dominance Red (C R C R ) X White (C W C W ) Snapdragons F 1 generation are all pink (C R C W ) F 2 generation is 1 red:2 pink:1 white Not blending, parental phenotype is recovered in the F 2.
Incomplete Dominance Red (C R C R ) X White (C W C W ) Roan (C R C W )
Codominance MN Blood Type: a single gene locus (B) at which two alleles (M and N) are possible. GenotypePhenotype B M B M M blood group B N B N N blood group B M B N MN blood group
Codominance The MN phenotype is not intermediate between M and the N phenotypes.
Codominance A,B,O Blood Type: a specific locus (I) at which there are three common alleles (A, B, and O). They are modifying enzymes. They modify cell surface glycolipids.
Codominance in Blood Types EnzymeFunction Aadds a galactosamine B adds a galactose O does not add anything
A, B, O, AB Blood Types GenotypePhenotype I A I A or I A I O + galactosamine, Blood Type A I B I B or I B I O + galactose Blood Type B I A I B + both Blood Type AB I O I O neither added, Type O
Compatible Blood Groups Donors and recipients must have matching cell surface molecules. If not “self,” the recipient will produce proteins called antibodies to agglutinate (clump together) the donated blood cells. The foreign cell surface molecule is an antigen.
Blood Group Compatibility Blood TypeAntibodies Produced Aanti-B Banti-A ABneither antibody (universal recipient) O anti-A and anti-B (universal donor)
Rh Factor in Humans Rh Blood Group: another cell surface marker on RBC’s controlled by > 7 closely linked genes. GenotypePhenotype R R or R rcell surface marker (about are Rh + 85%) rrlack molecule, Rh -
Rh Factor in Humans What happens when an Rh - female X Rh + male? Offspring is possibly Rh +. If fetal Rh + RBCs cross the placenta and treated as a foreign antigen. Anitbodies (IgG) cross the placenta and agglutinate fetal RBC’s- erythroblastosis fetalis Treat with Rhogam: anit-Rh antibodies and prevent maternal immune response.
Genetic Diseases can be Mendelian Dominant or Recessive
Autosomal Dominant Diseases Homozygotes and Heterozygotes can be phenotypically the same- both show disease phenotype. Lethal dominant diseases are less common. Why?
Autosomal Dominant Diseases Familial Hypercholesterolemia- most common; 1:500; 19p13.2-p13.1 Huntington’s Disease- production of an inhibitor of brain cell metabolism; degeneration of nervous system at middle age; lethal dominant; 1:10,000; 4p16.3
Achondroplasia- autosomal dominant Affects in 1:10,000. Heterozygotes have dwarf phenotype. Homozygosity is lethal.
Polydachtyly -dominant mutation at 13q21-q32, occurs only 1/400)
Autosomal Recessive Diseases Heterozygotes are phenotypically normal, called carriers. Only the homozygous recessive alleles are diseased. Lethal Recessive Diseases are more common. Why?
Cystic fibrosis-Autosomal Recessive Most common Caucasian genetic disease- 1: 2500 affected; 1:25 are carriers. Mutation in a chloride channel protein (CFTR). Leads to high [Cl - ]in extracellular fluid. Causes mucus to become thicker than normal-favors bacterial infections. Untreated condition- death by fifth year.
Tay-Sachs Disease Recessive lethal allele-dysfunctional hexosaminidase A; unable to metabolize gangliosides (lipids of the CNS). Lipids accumulate--> lead to neuron death and eventual death. Affects 1: 3600 European Jews. Only the homozygotes are affected and die.
Tay-Sachs Disease- Autosomal Recessive Why are only the homozygous people affected? In other words, why is this disease recessive? Answer: the Heterozygote produces about 1/2 the normal amount of enzyme--> they are phenotypically normal.
Genetic Diseases are Codominant at the Molecular Level Sickle-cell Disease: a single amino acid change at #6 (Glu-->Val) in the 146 a.a. chain of hemoglobin. Mutant form of hemoglobin deforms the RBCs at low [O 2 ]. Multiple Symptoms: anemia, clumping and clogging of RBCs (heart failure and CV disease), spleen and kidney damage.
The Genetics of Sickle-Cell GenotypePhenotype A + A + normal (9/10) A + A s Het. Carriers, usually normal, the two alleles are codominant; 1/10; resistance to malaria. A s A s severe disease 1/400 African-Americans
Dominance/Recessiveness Range from Complete--->Incomplete--- ---->Codominance. Reflect the functions of the enzymes encoded by the alleles and not one allele subduing or overpowering another. Dominance does not determine the relative frequency of alleles in a population.
Other Patterns of Inheritance Complex Gene Interactions
Multiple Alleles Possible for a Gene Incomplete Dominance or Codominance- Ex. Coat color in cattle; Red X White ---> Roan Ex. ABO blood type; the I A and I B are equally expressed--> AB blood type.
Pleiotropy When one gene or allele has multiple phenotypes (pleion= many). Ex. Sickle-cell allele has many symptoms: Breakdown of RBCs--> Anemia, Heart Failure, Physical Weakness Clumping of RBCs--> Brain Damage, Kidney and Spleen Damage.
Pleiotropy Often a gene functions in some other unknown way. Ex. Lucien Cuenot- tried to develop a true-breeding yellow- furred mouse. Y= dominant for yellow fur color. Unable to get a YY strain. Why?
Pleiotropic Effects of Y Yy (Yellow Fur Color, Dominant) Y allele YY (Lethal Development, Recessive)
Epistasis When a gene at one locus alters the phenotypic expression of another gene at a second locus.
Epistasis Ex. Coat Color in Mammals: One gene, the B locus: B = black or b = brown BB or Bb = both black, bb = brown Another gene, C, deposits pigment into hair CC or Cc = dominant for color cc = no pigment deposited, albino
Genetics of Coat Color in Mammals What do the offspring of a BbCc X BbCc (dihybrid) cross look like? 9 Black : 3 Brown : 4 Albino What would Mendel predict? 9 : 3: 3 :1
Another Example of Epistasis R. A. Emerson, 1918, Zea mays Crossed two pure-breeding strains that never expressed purple pigment (anthocyanin) in seed coat. All of the F 1 plants were purple! Crossed these F 1 plants--> 56% of F 2 purple, 44% were not. How?
Epistasis in Zea mays Dominant alleles encode functional enzymes and produce purple pigment. Recessive alleles encode nonfunctional enzymes. Requires BOTH dominant alleles for the purple phenotype.
Another Example of Epistasis- PTC Tasting Can two non-tasters produce a taster child? Answer: Yes! tt X tt --> Taster Offspring. I lied! This trait isn’t a simple dominance/recessive trait. Research suggests the phenotype is controlled by two genes.
Polygenic Traits These are not “either/or” characteristics, but a continuum or gradation. Quantitative Characters-quantitative variation indicates polygenic inheritance- an additive effect of two or more genes on a single phenotypic character. Converse of Pleiotropy.
Polygenic Traits Ex. Skin Color in Humans controlled by at least three separately inherited genes. Three Genes: A, B, C, dark-skin alleles, each contribute one “unit” of darkness and are incompletely dominant to the a, b, c alleles. AABBCC = very dark aabbcc = very light
Human Skin Color AaBbCc = intermediate skin color Alleles have cumulative effect; AaBbCc and AABbcc both make same three unit contribution to darkness. Cross AaBbCc X AaBbCc
AaBbCc X AaBbCc Skin Color aabbcc1/64 Very Light Aabbcc6/64 AaBbcc15/64 AaBbCc20/64Intermediate AABbCc15/64 AABBCc6/64 AABBCC1/64Very Dark
Polygenic Traits Quantitative Characteristics- give a bell-shaped curve, a normal distribution. Environmental Factors (sun exposure help smooth the curve also. Ex. Height and Weight
Multifactorial Inheritance Environmental factors interact with genes. Genotype may be a phenotypic range or possibilities- norm of reaction for the genotype. The variation is due to environmental factors.
Multifactorial Inheritance The norm of reaction may be small- Example: ABO Blood type. Or it may be very broad- Example: the Number of RBCs--> physical activity, altitude, health, the genes that control cell division.
Hydrangea Flowers - of the same genotype range in color from purple (alkaline soils) to pink (acidic soils) due to anthocyanin. Cardiovascular Disease- ApoE gene (apolipoprotein E) and the angiotensin genes affect cholesterol levels and blood pressure levels--> genetic predisposition + lifestyle factors such as diet, smoking, physical activity.