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Mendel and the Gene Idea PowerPoint Lectures for Biology, Seventh Edition Chapter 14 Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Points to Ponder • What is the genotype and the phenotype of an individual? • What are the genotypes for a homozygous recessive and dominant individuals and a heterozygote individual? • Be able to draw a punnett square for any cross (1-trait cross, 2-trait cross and a sex-linked cross). • What are Tay-Sachs disease, Huntington disease, sickle-cell disease, and PKU? • How are each of the above inherited? • What is polygenic inheritance? • What is a multifactorial trait? • What is sex-linked inheritance? • Name 3 X-linked recessive disorders. • What is codominance? • What is incomplete dominance? • What do you think about genetic profiling? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Gregor Mendel (1822-1884) Documented a particulate mechanism of inheritance through his experiments with garden peas Figure 14.1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings “particulate” inheritance – Mendel thought that parents pass on discrete heritable units, “genes” (Mendel referred to these as “factors”) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mendel’s experiments • Concept 14.1: Mendel used the scientific approach to identify some basic Laws of Inheritance • Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned and executed experiments Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Some genetic vocabulary – Gene: the basic unit of heredity in a living organism; a gene is a section of a chromosome that codes for a trait, or characteristic. – Alleles: alternate forms of a specific gene at the same position (locus) on a gene (e.g. allele for unattached earlobes and attached lobes); alleles occur in pairs Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • For each character, – An organism inherits two alleles, one from each parent – A genetic locus is actually represented twice, in diploid organisms Homologous chromosomes, one paternal, one maternal Allele for purple flowers Locus for flower-color gene Homologues are similar in size, centromere location, and in the genes that they carry Figure 14.4 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allele for white flowers Homologous pair of chromosomes Dominants and Recessives • If the two alleles at a locus differ – Then one, the dominant allele, determines the organism’s appearance – The other allele, the recessive allele, has no noticeable effect on the organism’s appearance (is “masked”) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Vocabulary review Homozygous: (aka “purebred” or “truebreeding”) have an identical set of alleles for a trait Heterozygous: hybrid; nonmatching alleles Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Understanding genotype & phenotype Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Genotype – specific genes for a particular trait written with symbols (example: EE, Ee, or ee) Phenotype – the physical or outward expression of the genotype egg E e E e E e sperm fertilization EE ee Ee growth and development EE unattached earlobe ee attached earlobe Allele Key E= unattached earlobes e= attached earlobes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ee unattached earlobe zygote Mendel’s Experimental, Quantitative Approach • Mendel chose to work with peas – Because they are available in many varieties – Because he could strictly control which plants mated with which Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • He started his experiments with varieties that were “true-breeding” (purebred lines isolated through selfpollination) = “P” generation • When Mendel crossed contrasting, true-breeding white and purple flowered pea plants – ALL of the offspring (F1 generation) were purple. Why? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Punnett Squares tutorial The Punnett square is a diagram that is used to predict an outcome of a particular cross or breeding experiment. It is named after Reginald C. Punnett, who devised the approach, and is used by biologists to determine the probability of an offspring having a particular genotype. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mendel’s Principle of Dominance and Recessiveness • Mendel reasoned that – In the F1 plants, only the purple flower “factor“ was affecting flower color (phenotype) in these hybrids – Purple flower color was dominant, and white flower color was recessive In such cases, the dominant allele “MASKS” the recessive Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Next, when Mendel crossed the purple F1 plants: WHAT DO YOU PREDICT THE COLOR RATIOS WOULD BE FOR THE F2 GENERATION? – Mendel found that most of the F2 plants had purple flowers, but some had white flowers – He found a repeatable ratio of about 3:1, purple to white flowers, in the F2 generation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Mendel observed the same pattern in many other pea plant characters • Mendel developed a hypothesis to explain the 3:1 inheritance pattern that he observed among the F2 offspring Table 14.1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Law of Segregation • The two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Segregation of Alleles (meiosis) • Does Mendel’s segregation model account for the 3:1 ratio he observed in the F2 generation of his numerous crosses? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Law of Independent Assortment • Independent assortment – Each pair of alleles segregates independently during gamete formation Animated version: http://www.sumanasinc.com/webcon tent/animations/content/independent assortment.html Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Possible gametes for TWO traits Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sex and variation • Crossing over prior to gamete formation increases variables • Independent assortment http://www.csuchico.edu/~jbell/Biol207/animations/assortment.html • Crossover animation http://www.csuchico.edu/~jbell/Biol207/animations/recombination.html Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The extent of variation • Not only does meiosis guarantee segregation and independent assortment of alleles, but crossing over also mixes up alleles on homologous chromosomes before distribution “Therefore, in humans with 23 pairs of chromosomes, a gamete (egg or sperm) could have 223 or 8,388,604 possible combinations of chromosomes from that parent. Any couple could have 223 × 223 or 70,368,744,177,644 (70 trillion) different possible children, based just on the number of chromosomes, not considering the actual genes on those chromosomes. Thus, the chance of two siblings being exactly identical would be 1 in 70 trillion. In addition, something called crossing over, in which the two homologous chromosomes of a pair exchange equal segments during synapsis in Meiosis I, can add further variation to an individual’s genetic make-up.” http://www.biology.clc.uc.edu/Courses/bio104/meiosis.htm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Dihybrid Crosses & Independent Assortment of alleles • Illustrates the inheritance of two characters • Produces four phenotypes in the F2 generation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The reality of inheritance • Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian genetics • The relationship between genotype and phenotype is rarely simple What about green eyes? Hazel eyes? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The genetics of eye color • At one locus (site=gene) there are two different alleles segregating: the B allele confers brown eye color and the recessive b allele gives rise to blue eye color. • At the other locus (gene) there are also two alleles: G for green or hazel eyes and g for lighter colored eyes. • The B allele will always make brown eyes regardless of what allele is present at the other locus. In other words, B is dominant over G. In order to have true blue eyes your genotype must be bbgg. If you are homozygous for the B alleles, your eyes will be darker than if you are heterozygous and if you are homozygous for the G allele, in the absence of B, then your eyes will be darker (more hazel) that if you have one G allele. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Extending Mendelian Genetics for a Single Gene • The inheritance of characters by a single gene – May deviate from simple Mendelian patterns – Exceptions to the “rules” are listed in the following slides Need practice? Try these “drag and drop” Punnett squares http://www.execulink.com/~ekimmel/mendel1a.htm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Spectrum of Dominance • Complete dominance – Occurs when the phenotypes of the heterozygote and dominant homozygote are identical PP pp Pp Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Incomplete dominance (aka “blended inheritance) • The phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties Example: Flower colors RR = red R’R’ = white RR’ = pink (intermediate pigmentation) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Spectrum of Dominance • In codominance – Two dominant alleles both affect the phenotype in separate, distinguishable ways • IAIB = The human blood group type AB is an example of codominance • RW = roan coat color in cattle or horses Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Multiple Alleles and Codominance • Most genes exist in populations – In more than two allelic forms • The ABO blood group in humans – Is determined by multiple alleles Table 14.2 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Frequency of Dominant Alleles • Dominant alleles – Are not necessarily more common in populations than recessive alleles – It really depends on whether a trait gives an individual an adaptive advantage, and is naturally selected. – Examples: type O blood (ii) recessive present in majority of population http://www.bio-medicine.org/biology-definition/Blood_type/#Frequency Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pleiotropy • Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. • The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets. • A classic example of pleiotropy is the human disease PKU (phenylketonuria). • This disease can cause mental retardation and reduced hair and skin pigmentation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid. • Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. • PKU is totally benign if a diet free from phenylalanine is maintained. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Gene Linkage • Sometimes, when genes are located close together on the same chromosome, they tend to be inherited together. • Which of Mendel’s Laws does this defy? • See linkage animation http://www.csuchico.edu/~jbell/Biol207/animations/linkage.html • A “classic” example of this is why cats with white fur and blue eyes are (more often than not) also deaf. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Extending Mendelian Genetics for Two or More Genes • Many traits (especially in complex organisms) – May be determined by two or more genes (polygenic) • In EPISTASIS “standing upon” – the phenomenon where the effects of one gene are modified by one or several other genes (which are sometimes called modifier genes). – A gene at one locus alters the phenotypic expression of a gene at a second locus Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings An example of epistasis in mice Here we see the effect the bb gene combo has on the C gene for the agouti (brownish) fur color in mice BbCc BbCc Sperm 1⁄ BC 4 1⁄ 4 bC 1⁄ 4 1⁄ Bc 4 bc Eggs 1⁄ 4 BC BBCC BbCC BBCc BbCc 4 bC BbCC bbCC BbCc bbCc cc combo = white fur 1⁄ C_ combo = black fur, unless bb “stands upon” it. Then you get agouti color. 1⁄ 1⁄ 4 Bc BBCc BbCc BBcc 4 bc BbCc bbCc Bbcc 9⁄ Figure 14.11 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 16 3⁄ 16 Bbcc 4⁄ bbcc 16 Other variations in gene expression • Incomplete Expressivity is seen in cases where individuals with the same genotypes may have, often for unknown reasons, variability in their phenotypes. – This is often seen in genetic diseases where one person with a disease such as diabetes may be very severely effected while another with the same allele may have a milder form of the disease. • Incomplete Penetrance is seen when an individual with a particular genotype does not express the phenotype. Again the reasons for this are not clearly understood. – For example, known mutations in the gene responsible for Huntington disease have “95% penetrance”, because 5% of those with the dominant allele for Huntington disease don't develop the disease and 95% do. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Beyond simple inheritance • Polygenic traits - two or more sets of alleles govern one trait Note that: Environmental effects can cause intervening phenotypes! – Each dominant allele codes for a product so these effects are additive – Results in a continuous variation of phenotypes – e.g. skin color ranges from very dark to very light AaBbCc aabbccAabbccAaBbccAaBbCc AABBCc AABBCC AABbCc 20⁄ 15⁄ 6⁄ 64 64 64 1⁄ Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings AaBbCc 64 Polygenic inheritance Number of Men Multifactorial trait – a trait that is influenced by both genetic and environmental factors e.g. skin color is influenced by sun exposure e.g. height can be affected by nutrition most are this height few 62 short Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 64 Courtesy University of Connecticut/Peter Morenus, photographer; few 66 68 Height in Inches 70 72 74 tall Genes are affected by Environment • While there is a strong genetic component in human height, the average height has increased over the past 50 years in developed countries. This is considered to be due to improved nutrition. • Likewise, a cotton plant may have the alleles necessary for high yields but if it doesn't receive enough water or fertilizer it cannot reach its genetic potential. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Example: – A phenotypic range of a particular genotype may be influenced by the environment Figure 14.13 Exact color often mirrors the pH of the soil; acidic soils produce blue flowers, neutral soils produce very pale cream petals, and alkaline soils results in pink or purple. This is caused by a color change of the flower pigments in the presence of aluminum ions which can be taken up into the flower. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Beyond simple inheritance Demonstrating environmental influences on phenotype Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Himalayan rabbit/Siamese cat coat color influenced by temperature • There is an allele responsible for melanin production that appears to be active only at lower temperatures • The extremities have a lower temperature and thus the ears, nose paws and tail are dark in color Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings © H. Reinhard/Arco Images/ Peter Arnold • Many human characters – Vary in the population along a continuum and are called “quantitative characters” • Humans are not convenient subjects for genetic research. Why? – However, the study of human genetics continues to advance – Advances in personal genomic testing Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A pedigree – • Is a family tree that describes the interrelationships of parents and children across generations Inheritance patterns of particular traits can be traced and described using pedigrees Ww ww Ww ww ww Ww WW or Ww Widow’s peak ww Ww Ww ww First generation (grandparents) Second generation (parents plus aunts and uncles) Ff FF or Ff Ff ff Third generation (two sisters) ww No Widow’s peak (a) Dominant trait (widow’s peak) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Attached earlobe ff ff Ff Ff Ff ff ff FF or Ff Free earlobe (b) Recessive trait (attached earlobe) Genetic mutations can lead to familial diseases • Somatic mutations — such as in skin cells as a result of sun exposure — tend to accumulate over the course of our lives, but are not typically passed on to children. • But other errors can occur in the DNA of cells that produce the eggs and sperm. These are called germline mutations and can be passed from parent to child. • If a child inherits a germline mutation from their parents, every cell in their body will have this error in their DNA. • Germline mutations are what cause diseases to run in families, and are responsible for hereditary diseases. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How does it work? • A gene is essentially a sentence made up of the bases A, T, G, and C that describes how to make a protein. • Any changes to those instructions can alter the gene's meaning and change the protein that is made, or how or when a cell makes that protein. • There are many different ways to alter a gene, just as there are many different ways to introduce typos into a sentence. In the following examples of some types of mutations, we use the sentence to represent the sample gene: THE FAT CAT ATE THE RAT (this is how the code should read) Here’s a handy table listing all the types of mutations: http://www.uvm.edu/~cgep/Education/Mutations.html Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Point mutation: a change in a single nucleotide Example 1: • A SUBSTITUTION mutation • occurs where one nucleotide base is replaced by another. – example • THE FAT CAT ATE THE RAT • THE FAT HAT ATE THE RAT Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Point mutations: types • Base (A,T,C,G) substitutions can lead to “Missense” or “Nonsense” mutations: Missense: a change in DNA sequence that changes the codon to a different amino acid. This can alter the protein enough to render it nonfunctional. Not all missense mutations are deleterious, some changes can have no effect. Because of the ambiguity of missense mutations, it is often difficult to interpret the consequences. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nonsense: a change in the genetic code that results in the coding for a stop codon rather than an amino acid. The shortened protein is generally non-function or its function is impeded. Point mutations can sometimes be “SILENT”. How does this change the protein that this gene codes for? More often than not, “third-base mutations” are silent. Why? Another example: Amino acid: leucine GAA GAG GAT GAC Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sickle-Cell Disease – Affects one out of 400 African-Americans – Is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells (shows seven out of the 146 amino acid units of normal hemoglobin) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sickle Cell • Symptoms include physical weakness, pain, organ damage, and even paralysis • Sickle-cell disease occurs more commonly in people (or their descendants) from parts of the world such as sub-Saharan Africa, where malaria is or was common, but it also occurs in people of other ethnicities. • This is because those with one or two alleles of the sickle cell disease are resistant to malaria since the red blood cells are not conducive to the parasites. • In areas where malaria is common there is a survival value in carrying the sickle cell genes. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sickle Cell Disease • Homozygous recessive individuals have sickle cell disease. • Heterozygous individuals are phenotypically normal, but exhibit a mild version of the disease; said to “carry” the trait for SC, but not actually have the disease (symptoms usually only apparent @ altitude or heavy exercise). • Homozygous dominant individuals are phenotypically normal. Genotypes: Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Electrophoresis of the hemoglobin protein shows: We see that homozygous normal people have one type of hemoglobin (A) and anemics have type S, which moves more slowly in the electric field. The heterozygotes have both types, A and S. In other words, there is codominance at the molecular level. Try this pedigree of familial inheritance of SC disease Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Point mutation: a change in a single nucleotide in a gene • Examples 2 & 3: – Insertion example • THE FAT CAT ATE THE RAT (original gene) • THE FAT CAT LAT ETH ERA T – Deletion example • THE FAT CAT ATE THE RAT (original gene) • THE FAT ATA TET HER AT These substitutions are known as “Frameshift Mutations” because they shift the reading frame of the genetic message (triplets) so that the protein may not be able to perform its function. Usually more serious than a substitution mutation. Why? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Follow this summary: Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Remember: not all mutations are bad! • A harmful mutation is a mutation that decreases the fitness of the organism. • Sometimes, mutations can change a gene form in a nonharmful, or even beneficial, way. • “Polymorphisms”: slight variations in a gene that make us different, ex: eye colors, blood types, etc. Are these good or bad? • A mutation may enable the mutant organism to withstand particular environmental stresses better than non-mutant organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. This is how populations EVOLVE over time. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Many mutations are neutral • A neutral mutation has no harmful or beneficial effect on the organism. • Many of these mutations occur in the noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. • More than 98% of the human genome does not encode protein sequences. We often call this “junk DNA” (extra). – Why are these “junk” sequences more likely to vary between individuals? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chromosome Mutations • A chromosome mutation is an unpredictable (spontaneous) change that occurs in a chromosome. • These changes are most often brought on by problems that occur during meiosis (cell division that makes gametes) or by mutagens (chemicals, radiation, etc.). • Chromosome mutations can result in changes in the number of chromosomes in a cell or changes in the structure of a chromosome. • Usually MUCH more serious than a gene mutation. Why? Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Changes in chromosome number or structure (a) A deletion removes a chromosomal segment. A B C D E F G H (b) A duplication repeats a segment. A B C D E F G H (c) An inversion reverses a segment within a chromosome. A B C D E F G H d) A translocation moves a segment from one chromosome to another, nonhomologous one. A B C D E F G H • In a “reciprocal translocation", the most common type, nonhomologous chromosomes exchange fragments. Deletion Duplication Inversion A B C E F G H A B C B C D E A D C B E F G H F G H M N O C D E F G H Reciprocal translocation M N O P Q R A B P Q R What occurs in a “nonreciprocal translocation”? • 58 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Test your knowledge Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Changes in Chromosomal Structure (animation) • http://glencoe.mcgrawhill.com/sites/9834092339/student_view0/chapter24/chang es_in_chromosome_structure.html • The Consequence of Inversion (animation) • http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/ free/0072437316/120082/bio33.swf::The%20Consequence %20of%20Inversion Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Recessively Inherited Autosomal Disorders • Many genetic disorders – Are inherited in a recessive manner (aa) – So, most affected individuals are homozygous (dual inheritance) – AA, Aa are normal phenotype, in this case • Recessively inherited disorders – • Show up only in individuals homozygous for the allele Carriers – Are heterozygous individuals who carry the recessive allele but are phenotypically normal Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cystic Fibrosis (recessive mutation in CFTR gene) • Symptoms of cystic fibrosis include – Mucus buildup in the some internal organs – Abnormal absorption of nutrients in the small Lung tissue from a cystic fibrosis intestine patient, showing extensive destruction as a result of obstruction and infection. Cl - H2O nebulizer defective channel percussion vest thick mucus Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phenyketonuria PKU is an autosomal recessive genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. Amino acids are the building blocks for body proteins. • In 'classic PKU', the enzyme (phenylalanine hydroxylase), that breaks down phenylalanine is completely or nearly completely deficient. (PAH gene, 12q23.2 ) • This enzyme normally converts phenylalanine to another amino acid, tyrosine. Without this enzyme, phenylalanine and its' breakdown chemicals from other enzyme routes, accumulate in the blood and body tissues. • Infants are born “normal” but if not treated, severe brain problems, such as mental retardation and seizures, will occur. • Thus, this disease is GREATLY influenced by environmental factors: “multifactorial” Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other autosomal recessive disorders • Tay-Sachs disease • Albinism • Hemochromatosis types 1-3: the most common genetic disease in Europe. You can watch this animation on inheritance of the HFE allele: https://www.koshland-sciencemuseum.org/sites/all/exhibits/exhibitdna/inh05.jsp Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Dominantly Inherited Disorders • Some human disorders – Are due to dominant alleles One example is achondroplasia – A form of dwarfism that is lethal when homozygous for the dominant allele (DD) Figure 14.15 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Dominant allele • Huntington’s disease – Is a degenerative disease of the nervous system – Has no obvious phenotypic effects until about 35 to 40 years of age Lake Maracaibo, Venezuela Village pedigree Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sex-linked inheritance X-linked disorders • More often found in males than females because recessive alleles are always expressed • Most X-linked disorders are recessive: – Color blindness: most often characterized by redgreen color blindness – Duchenne’s muscular dystrophy (DMD): characterized by wasting of muscles and death by age 20 – Fragile X syndrome: most common cause of inherited mental impairment – Hemophilia: characterized by the absence of particular clotting factors that causes blood to clot very slowly or not at all Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sex-linked inheritance X-linked disorders Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. B X X B B b X Y grandfather B b X X daughter X Y B b X Y X X b X Y B X Y B X X B B X X b b X Y grandson B B X X B b X X b b X X B X Y b X Y Key =Unaffected female =Carrier female =Color-blind female =Unaffected male =Color-blind male X-linked Recessive Disorders • More males than females are affected. • An affected son can have parents who have the normal phenotype. • For a female to have the characteristic, her father must also have it. Her mother must have it or be a carrier. • The characteristic often skips a generation from the grandfather to the grandson. • If a woman has the characteristic, all of her sons will have it. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings b Mating of Close Relatives • Matings between relatives are called “consanguineous” matings • Can increase the probability of the appearance of a genetic disease (especially harmful recessive homozygotes) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sex-linked inheritance X-linked disorders: Hemophilia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Key Unaffected male Hemophiliac Unaffected female Carrier Queen Victoria Prince Albert 4 children of 9 are shown Victoria Frederick III (Germany) Alice Louis IV (Hesse) Princess Helena of Waldeck Leopold (died at 31) Beatrice Prince Henry of Battenberg 12 children of 26 are shown Henry Irene Frederick Alexandra (died at 3) Nicholas II (Russia) Alice Alexander Alfonso XII Victoria (Earl of (Spain) Athlone) 6 children of 34 are shown Waldemar (died at 56) Henry (died at 4) Alexei (murdered) Rupert (died at 21) Alfonso Gonzalo (died at 31) (died at 20) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (queen): © Stapleton Collection/Corbis; (prince): © Huton Archive/Getty Images Leopold (died at 32) Multifactorial Disorders • Many human diseases – Have both genetic and environment components • Examples include – Heart disease and cancer – Try this interactive family pedigree (nicotine addiction) http://learn.genetics.utah.edu/units/addiction/genetics/pi.cfm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Testing and Counseling • Genetic counselors – Can provide information to prospective parents concerned about a family history for a specific disease Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Counseling Based on Mendelian Genetics and Probability Rules • Using family histories – Genetic counselors help couples determine the odds that their children will have genetic disorders Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tests for Identifying Carriers • For a growing number of diseases – Tests are available that identify carriers and help define the odds more accurately Fetal Testing • In amniocentesis – The liquid that bathes the fetus is removed and tested • In chorionic villus sampling (CVS) – A sample of the placenta is removed and tested Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Prenatal Genetic Screening Genetic Screening (karyotyping) is possible, prenatally Amniocentesis, @ 14-16 weeks Chorionic villus sampling (CVS), @ 9-14 weeks 75 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept: Some inheritance patterns are exceptions to the standard chromosome theory • Epigenetics – Functional modifications to the genome that do not involve a change in the nucleotide sequence. – Environmental factors can alter the way our genes are expressed, making even identical twins different. – Examples of such modifications are DNA methylation and histone modification, both of which serve to regulate gene expression without altering the underlying DNA sequence. http://learn.genetics.utah.edu /content/epigenetics/ Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genomic Imprinting What Is Imprinting? • For most genes, we inherit two working copies -- one from mom and one from dad. But with imprinted genes, we inherit only one working copy. Depending on the gene, either the copy from mom or the copy from dad is epigenetically silenced. Silencing usually happens through the addition of methyl groups during egg or sperm formation. The epigenetic tags on imprinted genes usually stay put for the life of the organism. But they are reset during egg and sperm formation. Regardless of whether they came from mom or dad, certain genes are always silenced in the egg, and others are always silenced in the sperm. http://learn.genetics.utah.edu/content/epigenetics/imprinting/ Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genomic imprinting Involves the silencing of certain genes that are “stamped” with an imprint during gamete production Normal Igf2 allele (expressed) Paternal chromosome When a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size. But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype. Maternal chromosome Normal Igf2 allele Wild-type mouse with imprint (normal size) (not expressed) (a) A wild-type mouse is homozygous for the normal igf2 allele. Normal Igf2 allele Paternal Maternal Mutant lgf2 allele Normal size mouse Mutant lgf2 allele Paternal Maternal Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Normal Igf2 allele with imprint Dwarf mouse In mammals the phenotypic effects of certain genes depend on which allele is inherited from the mother and which is inherited from the father Genes located outside the nucleus also have influence • Extranuclear genes – • Are genes found in organelles in the cytoplasm The inheritance of traits controlled by genes present in the chloroplasts (ctDNA) or mitochondria (mtDNA) – Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg Figure 15.18 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In Humans: • Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATP – Examples of mitochondrial DNA diseases: • Leber's hereditary optic atrophy - causes progressive visual impairment • Kearns-Sayre disease • Progressive external ophthalmoplegia • Myoclonus epilepsy • MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) – Mitomap - A human mitochondrial genome database Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings