Principles Of Genetics (Laboratory) PDF

PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM MENDELIAN GENETICS two easily distinguished expressions, or phenotypes. (TRANSMISSION GENETICS) GREGOR MENDEL...

PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM MENDELIAN GENETICS two easily distinguished expressions, or phenotypes. (TRANSMISSION GENETICS) GREGOR MENDEL DEFINITION OF TERMS - 144 years ago, 1866, first significant - Allele: One alternative of a pair or group of insights into mechanisms of heredity genes that could occupy a specific - Gregor Johann Mendel, Augustinian monk position on a chromosome. in Brno (Czech Rep.) - Chromosome: A linear strand of DNA - Garden pea, Pisum sativum harboring many genes. - Discrete units of inheritance predict - Compound Heterozygote: An individual behavior during gamete formation with two different recessive alleles for the - 7 visible features (unit characters), each same gene. represented by two contrasting forms or - DNA: Deoxyribonucleic acid; the molecule traits in which genetic information is encoded. - Dominant: An allele producing the same phenotypic effect whether inherited heterozygously or homozygously; an allele that "masks" a recessive allele. - Gene: A unit of genetic information that occupies a specific position on a chromosome and comes in multiple versions called alleles. - Genotype: The genetic constitution of an organism. - Heterozygous: Having a genotype with two different and distinct alleles for the same trait. - Homozygous: Having a genotype with two of the same alleles for a trait. - Mendel bred pea plants to describe units - Mutant Phenotype: a variant of a gene’s of inheritance, “elementen,” that pass traits expression that arises when the gene from generation to generation. undergoes a change, or mutation. - Mendel’s laws apply to any diploid species. - Phenotype: The physical or observable characteristics of an organism. - Peas are ideal for probing heredity because they are easy to grow, develop - Recessive: An allele producing no quickly, and have many traits that take one phenotypic effect when inherited of two easily distinguishable forms. heterozygously and only affecting the phenotype when inherited homozygously; an allele "masked" by a dominant allele. CHARACTERISTICS OF SINGLE-GENE INHERITANCE - Inherited illnesses caused by single genes differ from other types of illnesses in several ways. In families, we can deduce the probability that a particular person has inherited a single-gene disease by considering how he or she is related to an - Gregor Mendel studied the transmission of affected relative. seven traits in the pea plant. Each trait has - The sisters in the family described in the chapter opener, for example, each had a 1 SOFIA BROSO PYN3 1 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM in 2 chance of inheriting their father’s - In contrast, CF is autosomal recessive, Huntington disease. which means that the disease affects both - In contrast, an infectious disease requires sexes and can “skip” generations through that a pathogen pass from one person to carriers, who do not have symptoms. another, which is much less predictable. - Today, genetic tests, including exome and - A second distinction of single-gene genome sequencing, reveal which diseases is that tests can sometimes single-gene health conditions we have, predict the risk of developing symptoms. carry, or may develop. - This is possible because all cells harbor the - Tests of “trios” consisting of sick children mutation, if the person has inherited it. and their parents can reveal whether the - A person with a parent who has child inherited two disease-causing Huntington disease can have a blood test mutations from carrier parents, or whether that detects the mutation at any age, even a dominant mutation arose anew, termed though the disease affects the brain, not “de novo.” the blood. - This predictive power is a characteristic of Single-gene traits and diseases are called a particular gene, and for a gene with less “Mendelian” in honor of Gregor Mendel, who first predictive power, a genetic test may derived the two laws of inheritance that determine indicate increased risk of developing how these traits are transmitted from one symptoms but not the near certainty that generation to the next. occurs with the HD mutation. This predictive ability is called penetrance. SINGLE-GENE INHERITANCE IS RARE - Mendel’s first law addresses traits and - A third feature of single-gene diseases is illnesses caused by single genes, which that they may be much more common in are also called Mendelian or some populations than others. monofactorial. - Genes do not like or dislike certain types of - Single-gene diseases, such as sickle cell people; rather, mutations stay in certain disease and muscular dystrophy, are rare populations because we tend to have compared to infectious diseases, children with people similar to ourselves. cancer,and multifactorial diseases. - While it might not seem politically correct - The actions of at least one gene and the to offer a “Jewish genetic disease” screen, environment cause multifactorial diseases. it makes biological and economic - Many single-gene diseases affect fewer sense—several diseases are much more than 1 in 10,000 individuals. common in that population. - The single gene controls trait transmission, but other genes and the environment - A fourth characteristic of a genetic affect the degree of the trait or severity of disease is that it may be “fixable” by the illness. compensating for the abnormal instructions, such as by providing a MODES OF INHERITANCE missing enzyme or clotting factor. - Modes of inheritance are rules that explain the common patterns of single-gene - Single-gene diseases such as HD and transmission, and are derived from cystic fibrosis (CF) affect families in Mendel’s laws. patterns, termed modes of inheritance. - Knowing the mode of inheritance makes it - Knowing these patterns makes it possible possible to calculate the probability that a to predict the risks that people related in particular couple will have a child who particular ways have inherited the family’s inherits a particular condition. mutation. - The way that a trait is passed depends on - HD is autosomal dominant, which means whether the gene that determines it is on that it affects both sexes and appears an autosome or on a sex chromosome, every generation. and whether the allele is recessive or dominant. SOFIA BROSO PYN3 2 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM - This experiment is called a monohybrid AUTOSOMAL DOMINANT cross because it follows one trait and the - In autosomal dominant inheritance, a trait self-crossed plants are hybrids. can appear in either sex because an autosome carries the gene. - parents are true breeding individuals (P1) – parental generation - If a child has the trait, at least one parent - F1 or first filial generation – offspring of P1 also has it. - F2 or second filial generation – individuals - Autosomal dominant traits do not skip resulting from selfed F1 individuals generations because if no offspring inherit - reciprocal crosses were conducted, same the mutation in one generation, results obtained used to illustrate Law of transmission stops. Segregation - Huntington disease is an autosomal dominant condition. LAW OF SEGREGATION Example: - Gametes distribute “elementen” because these cells physically link generations. - Paired sets of elementen separate as gametes form. When gametes join at fertilization, the elementen combine anew. - Mendel reasoned that each elementen was packaged in a separate gamete. - If opposite-sex gametes combine at random, he could mathematically explain the different ratios of traits produced from his pea plant crosses. - Mendel’s idea that elementen separate in the gametes would later be called the law of segregation. When one parent has an autosomal dominant - When Mendel’s ratios were seen in several condition and the other does not, each offspring species in the early 1900s, just when has a 50 percent probability of inheriting the chromosomes were being discovered, it mutant allele and the condition. In the family from became apparent that elementen and the chapter opener, Karl was the “Aa” parent and chromosomes had much in common. Janethe “aa” parent. Each of their daughters faced the 1 in 2 probability of inheriting - Both paired elementen and pairs of Huntington's Disease. chromosomes separate at each generation and are transmitted—one from each parent—to offspring. AUTOSOMAL RECESSIVE - Both are inherited in random - A trait can appear in either sex. combinations. Chromosomes provided a - Affected individuals have a homozygous physical mechanism for Mendel’s recessive genotype, whereas in hypotheses. heterozygotes (carriers) the wild type allele - In 1909, English embryologist William masks expression of the mutant allele. Bateson renamed Mendel’s elementen - A person with cystic fibrosis, for example, genes (Greek for “give birth to”). inherits a mutant allele from each carrier parent. PUNNETT SQUARE - A Punnett square represents how genes in MONOHYBRID CROSS gametes join if they are on different MONOHYBRID CROSS chromosomes. - The different types of gametes of one - involves one pair of contrasting traits parent are listed along the top of the - Mendel conducted up to 70 hybrid self-crosses for each of the seven traits SOFIA BROSO PYN3 3 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM square, with those of the other parent by its phenotype—that is, a short plant is listed on the left-hand side. always tt. - Each compartment displays the genotype - The homozygous recessive is a “known” that results when gametes that that can reveal the unknown genotype of correspond to that compartment join. another individual to which it is crossed. TEST CROSS - Crossing an individual of unknown genotype with a homozygous recessive individual is called a test cross. - The logic is that the homozygous recessive is the only genotype that can be identified - Breeding a tall pea plant with homozygous recessive short plants reveals whether the - tall plant is true-breeding (TT) or non-true-breeding (Tt). - Punnett squares usually indicate only the alleles. SOFIA BROSO PYN3 4 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM SOLVING A PROBLEM IN FOLLOWING A SINGLE GENE The following general steps can help to solve a problem based on the inheritance of a single-gene trait: 1. List all possible genotypes and phenotypes for the trait. 2. Determine the genotypes of the individuals in the first (P1) generation. Use information about those individuals’ parents. 3. After deducing genotypes, derive the possible alleles in gametes each individual produces. 4. Unite these gametes in all combinations to reveal all possible genotypes. Calculate ratios for the F1 generation. 5. To extend predictions to the F2 generation, use the genotypes of the specified F1 individuals and repeat steps 3 and 4. SOFIA BROSO PYN3 5 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM DIHYBRID CROSS - natural extension of the monohybrid cross - 2 characters are examinesimultaneously - also a two-factor cross - showed the Law of Independent Assortment SOFIA BROSO PYN3 6 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM - Mendel looked at seed shape, which was either round or wrinkled (determined by the R gene), and seed color, which was either yellow or green (determined by the Y gene). When he crossed true-breeding plants that had round, yellow seeds to true-breeding plants that had wrinkled, green seeds, all the progeny had round, yellow seeds. - These offspring were double heterozygotes, or dihybrids, of genotype RrYy. - From their appearance, Mendel deduced that round is dominant to wrinkled, and yellow to green. - Mendel then crossed each plant from the third generation to plants with wrinkled, green seeds (genotype rryy). - These test crosses established whether each plant in the third generation was true-breeding for both genes (genotypes RRYY or rryy), true-breeding for one gene but heterozygous for the other (genotypes RRYy, RrYY, rrYy, or Rryy), or heterozygous for both genes (genotype RrYy). - Mendel could explain the 9:3:3:1 proportion of progeny classes only if one gene does not influence transmission of the other. - Each parent would produce equal numbers of four different types of gametes: RY, Ry, rY, and ry. - Each of these combinations has one gene for each trait. - A Punnett square for this cross shows that the four types of seeds: 1. round, yellow (RRYY, RrYY, RRYy, and RrYy), 2. round, green (RRyy and Rryy), 3. wrinkled, yellow (rrYY and rrYy), and 4. wrinkled, green (rryy) are present in the ratio 9:3:3:1, just as Mendel found. SOFIA BROSO PYN3 7 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM LAW OF INDEPENDENT ASSORTMENT - The law of independent assortment states that for two genes on different chromosomes, the inheritance of one gene does not influence the chance of inheriting the other gene. - The two genes are said to “independently assort” because they are packaged into gametes at random - The independent assortment of genes carried on different chromosomes results from the random alignment of chromosome pairs during metaphase of meiosis I. - An individual of genotype RrYy, for example, manufactures four types of gametes, containing the dominant alleles of both genes (RY), the recessive alleles of both genes (ry), and a dominant allele of one with a recessive allele of the other (Ry or rY). - The allele combination depends upon which chromosomes are packaged together in a gamete—and this happens at random. SAMPLE PROBLEMS 1. Mendel crossed peas having round seeds enclosed in full pods with wrinkled seeds enclosed in constricted pods. All F1 plants are round seeds enclosed on full pods. Diagram this cross through the F2 generation. a. Nature of seed (Round, W vs wrinkled, w) Nature of pod (Full, C vs constricted, c) b. All F1 plants are round seeds, enclosed on full pods c. Diagram the cross through the F2 SOFIA BROSO PYN3 8 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM dominant over vestigial wings. Work the following crosses through the F2 generation and determine the GR and PR ratios for each generation. Assume that P1 individuals are homozygous. a. gray, long x ebony, vestigial b. gray, vestigial x ebony, long c. gray. Long x gray, vestigial Body color (Gray, E vs ebpny, e) Wing length (Long, V vs vestigial, v) Work the following crosses through the F2 generation and determine the GR and PR ratios for each generation. Assume that P1 individuals are homozygous. a. gray, long x ebony, vestigial EEVV x wwvv b. gray, vestigial x ebony, long Eevv x wwVV c. gray. Long x gray, vestigial EEVV x EEvv 2. In Drosophila, gray body color is dominant over ebony body color, while long wings are SOFIA BROSO PYN3 9 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM BEYOND MENDEL’S LAWS EXAMPLES - In humans, early-acting lethal alleles WHEN GENE EXPRESSION APPEARS TO ALTER cause spontaneous abortion. MENDELIAN RATIOS - When both parents carry a recessive lethal - When transmission patterns of a visible allele for the same gene, each pregnancy trait do not exactly fit autosomal recessive has a 25 percent chance of spontaneously or autosomal dominant inheritance, aborting—that is, 25 percent of embryos Mendel’s laws are still operating. The are homozygous recessive. They do not underlying genotypic ratios persist, but develop further, and therefore this geno- other factors affect the phenotypes. type is not seen in any person. - This chapter considers three general phenomena that seem to be exceptions to - An example of a lethal genotype in Mendel’s laws, but are actually not: humans is achondroplastic dwarfism, - gene expression which has the distinct phenotype of a long - mitochondrial inheritance trunk, short limbs, and a large head - linkage. bearing a flat face - In several circumstances, phenotypic - It is an autosomal dominant trait, but is ratios appear to contradict Mendel’s laws, most often the result of a spontaneous but they do not. (new) mutation. - Each child of two people with achondroplasia has a one in four chance LETHAL ALLELE COMBINATIONS of inheriting both mutant alleles; however, - A genotype (allele combination) that because such homozygotes are not seen, this genotype is presumed to be lethal. causes death is, by strict definition, lethal. - Each child therefore faces a 2/3 probability - Death from genetic disease can occur at of having achondroplasia and a 1/3 any stage of development or life. probability of being of normal height, - In a population and evolutionary sense, a illustrating conditional probability. lethal genotype has a more specific - Homozygotes for achondroplasia meaning—it causes death before the mutations in other species cannot breathe because the lungs do not have room to individual can reproduce, which prevents inflate. passage of mutations to the next - The mutation is in the gene that encodes a generation. receptor for a growth factor. Without the receptor, growth is severely stunted. EXAMPLE: MULTIPLE ALLELES - A person has two alleles for any autosomal gene—one part of each homologous chromosome. - A gene can exist in more than two allelic forms in a population because it can mutate in many ways. - That is, the sequence of hundreds of DNA bases that makes up a gene can be altered in many ways - Different allele combinations can produce variations in the phenotype. - The more alleles, the more variations of the phenotype are possible. - An individual with two different mutant alleles for the same gene is called a compound heterozygote. SOFIA BROSO PYN3 10 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM DIFFERENT DOMINANCE RELATIONSHIPS - The sugar is an antigen, a molecule that - Incomplete Dominance the immune system recognizes and - Codominant responds to. INCOMPLETE DOMINANCE - People in blood group A have an allele that - In incomplete dominance, the encodes an enzyme that adds a piece to a heterozygous phenotype is intermediate certain sugar attached to the plasma between that of either homozygote. membrane, producing antigen A. - Enzyme deficiencies in which a threshold - In people with blood type B, the allele and level is necessary for health illustrate both its encoded enzyme are slightly different, complete and incomplete dominance. which places a different piece on the sugar, producing antigen B. EXAMPLES - People in blood group AB have both - For example, Tay-Sachs disease displays antigen types. complete dominance because the - Blood group O results from yet a third allele heterozygous (carrier) is as healthy as a of this gene. It is missing just one DNA homozygous dominant individual. nucleotide, but this changes the encoded - However, the heterozygote has an enzyme in a way that removes the sugar intermediate level of enzyme between the chain from its final piece homozygous dominant (full enzyme level) and homozygous recessive (no enzyme). - As a result, type O red blood cells do not - Half the normal amount of enzyme is have either A or B antigens. sufficient for health, which is why at the whole-person level, the wild type allele is completely dominant. - The A and B alleles are codominant, and both are completely dominant to O. - Considering the genotypes reveals how - Familial hypercholesterolemia (FH) is an these interactions occur. example of incomplete dominance that can be observed in carriers on both the - In the past, ABO blood types have been molecular and whole-body levels. described as variants of a gene called “I,” - A person with two disease-causing alleles which stands for isoagglutinin. does not have receptors on liver cells that take up the low-density lipoprotein (LDL) - The three alleles are IA, IB, and i. form of cholesterol from the bloodstream, - People with blood type A have antigen A so it builds up. on the surfaces of their red blood cells, and - A person with one disease-causing allele has half the normal number of receptors. may be of genotype IAIA or IAi. - Someone with two wild type alleles has the - People with blood type B have antigen B normal number of receptors. on their red blood cell surfaces, and may be of genotype IBIB or IBi. CODOMINANT - People with the rare blood type AB have - Different alleles that are both expressed in both antigens A and B on their cell a heterozygote are codominant. surfaces, and are genotype IAIB. - The ABO blood group system is based on - People with blood type O have neither the expression of codominant alleles. antigen, and are genotype ii. - Blood types are determined by the patterns of molecules on the surfaces of red blood cells. - Most of these molecules are proteins embedded in the plasma membrane with attached sugars that extend from the cell surface. - Blood types are determined by the patterns of cell surface on RBCs. SOFIA BROSO PYN3 11 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM EPISTASIS - Mendel’s laws can appear not to operate when one gene masks or otherwise affects the phenotype of another. - It refers to interaction between different genes, not between the alleles of the same gene. - A gene that affects the expression of another is called a modifier gene. - When one gene affects the expression of a second gene - In epistasis, the blocked gene is expressed (transcribed into RNA) normally, but the protein product of the modifier gene inactivates it, removes a structure needed for it to contribute to the phenotype, or otherwise counteracts its effects. The IA and IB alleles of the I gene are codominant, but they follow Mendel’s law of segregation. These Punnett squares show the genotypes that could EXAMPLES result when a person with type A blood has - A familiar epistatic interaction is albinism, children with a person with type B blood. in which one gene blocks the action of genes that confer color. - A blood type called the Bombay phenotype also illustrates epistasis. - It results from an interaction between a gene called H and the I gene that confers ABO blood type. - The H gene controls the placement of a molecule to which antigens A and B attach on red blood cell surfaces. - A person of genotype hh can’t make that molecule, so the A and B antigens cannot attach to red blood cell surfaces. - The A and B antigens fall off and the person tests as type O, but may be any ABO genotype. - Epistasis can explain why siblings who inherit the same disease can suffer to differing degrees. - One study examined siblings who both inherited spinal muscular atrophy (SMA) type 1, in which nerves cannot signal muscles. - The muscles weaken and atrophy, usually ABO blood types illustrate codominance. proving fatal in early childhood. ABO blood types are based on antigens on red blood cell surfaces. This depiction greatly - The mutation encodes an abnormal exaggerates the size of the A and B antigens. protein that shortens axons, which are the Genotypes are in parentheses. extensions on nerve cells that send messages. SOFIA BROSO PYN3 12 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM - Some siblings who inherited the SMA - Anything that shows less than 100% genotype, however, never developed penetrance is an example of incomplete symptoms. penetrance - They can thank a variant of another gene, - Why incomplete penetrance? plastin 3, which increases production of - Epigenetic factors the cytoskeletal protein actin that extends - Some genes can up or axons. downregulate rates of transcription - Because the healthy siblings inherited the - Polydactyly is incompletely penetrant. ability to make extra long axons, the - Some people who inherit the dominant axon-shortening effects of SMA were not allele have more than five digits on a hand harmful. or foot. - Yet others who must have inherited the PENETRANCE AND EXPRESSIVITY allele because they have an affected - The same genotype can produce different parent and child have ten fingers and ten degrees of a phenotype in different toes. individuals because of influences of other - Penetrance is described numerically. If 80 genes, as well as environmental influences of 100 people who inherit the dominant such as nutrition, exposure to toxins, and polydactyly allele have extra digits, the stress. genotype is 80 percent penetrant. - Two terms describe the degrees of expression of a single gene. - A phenotype is variably expressive if - Penetrance refers to the symptoms vary in intensity among percentage of individuals who have different people. a particular genotype who have the - One person with polydactyly might have associated phenotype. All or None an extra digit on both hands and a foot, - Expressivity refers to variability in but another might have just one extra severity of a phenotype, or the fingertip. extent to which the gene is - Polydactyly is both incompletely penetrant expressed. and variably expressive. - An allele combination that produces a FACTORS THAT MAY INFLUENCE THE phenotype in everyone who inherits it is EXPRESSION OF MOST GENES (BECAUSE completely penetrant. GENES DO NOT ACT ALONE) - A disease-causing gene shows 100% if all 1. Nutrition individuals who have this gene develop the 2. Exposure to Toxin associated trait or condition. 3. Other illnesses - Huntington disease is nearly completely 4. Other genes penetrant. It is a dementia that is genetically inherited as an The above mentioned factors can influence same autosomal-dominant trait with a complete allele combination thus producing different lifetime penetrance degree of phenotype in different individuals - Almost all people who inherit the mutant allele will develop symptoms if they live PLEIOTROPY long enough. Complete penetrance is - A single-gene disease with many symptoms, or a gene that controls several rare. functions or has more than one effect, is termed pleiotropic. - A genotype is incompletely penetrant if - Occurs when one gene influences two or some individuals do not express the more seemingly unrelated phenotypic phenotype (have no symptoms). traits - Genotype is present but the phenotype is - A mutation in a pleiotropic gene may have not observable an effect on several traits simultaneously - Such conditions can be difficult to trace through families because people with SOFIA BROSO PYN3 13 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM different subsets of symptoms may - Deafness appear to have different diseases. - Albinism - On a molecular level, pleiotropy occurs - Cleft Palate when a single protein affects different - Poor Blood Clotting body parts, participates in more than one biochemical reaction, or has different EXAMPLES effects in different amounts. - The different forms of Leber congenital amaurosis arise because there are many - Molecular Gene Pleiotropy: occurs when ways that a mutation can disrupt the the gene product interacts with multiple functioning of the rods and cones, the cells other proteins or catalyzes multiple that provide vision. reactions. - If a man who is homozygous recessive for - Developmental Pleiotropy: occurs when a mutation in one of the genes that causes mutations have multiple effects on the the condition has a child with a woman resulting phenotype. who is homozygous recessive for a - Selectional Pleiotropy: occurs when the different gene, then the child would not resulting phenotype has multiple effects inherit either form of blindness because he on fitness (perhaps depending on age, or she would be heterozygous for both gender, etc.) genes. EXAMPLES - Consider osteogenesis imperfecta, in - Consider Marfan syndrome. The most which abnormal collagen causes fragile common form of this autosomal dominant bones. condition is a defect in an elastic - Before a second causative gene was discovered, some parents of children who connective tissue protein called fibrillin. were brought to the hospital with frequent - The protein is abundant in the lens of the fractures and who did not have a mutation eye, in the aorta (the largest artery in the in the one known gene were accused of body, leading from the heart), and in bones child abuse. of the limbs, fingers, and ribs. - The symptoms are lens dislocation, long - Today eight genetically distinct forms of limbs, spindly fingers, and a caved-in chest the disease are recognized. - The most serious symptom is a weakening in the aorta, which can suddenly burst. - Eleven biochemical reactions lead to blood - If the weakening is detected early, a clot formation. synthetic graft can replace the section of - Clotting disorders may result from artery wall and save the person’s life. mutations in the genes that specify any GENETIC HETEROGENEITY enzymes that catalyze these reactions, - Mutations in different genes that produce leading to several types of bleeding the same phenotype lie behind genetic disorders. heterogeneity. - It can occur when genes encode enzymes or other proteins that are part of the same PHENOCOPIES biochemical pathway, or when proteins - An environmentally caused trait that affect the same body part, such as the appears to be inherited is a phenocopy. visual loss. - Such a trait can either produce symptoms - Genetic heterogeneity may make it appear that resemble those of a known that Mendel’s laws are not operating, even single-gene disease or mimic inheritance though they are. patterns by affecting certain relatives. - A phenomenon wherein different genes - It is not a type of mutation, as it is can produce identical phenotypes; non-hereditary contrast to pleiotropy; multiple gene - Trait caused by the environment that abnormalities appears inherited. - Individuals with identical phenotypes may reflect different genetic causes: SOFIA BROSO PYN3 14 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM EXAMPLES - In the rare instances when mitochondria from sperm enter an oocyte, they are usually selectively destroyed early in - For example, the limb birth defect caused development. by the drug thalidomide is a phenocopy of - Pedigrees that follow mitochondrial genes the rare inherited illness phocomelia. therefore show a woman passing the trait - Physicians recognized the environmental to all her children, whereas a male cannot disaster when they began seeing many pass the trait to any of his children born with what looked like phocomelia. - DNA in the mitochondria differs - A birth defect caused by exposure to a functionally from DNA in the nucleus in widely used teratogen was more likely than several ways: a sudden increase in incidence of a rare - MtDNA does not cross over. inherited disease. - It mutates faster than DNA in the nucleus because fewer types of - An infection can be a phenocopy if it DNA repair are available and affects more than one family member. DNA-damaging oxygen free - Children who have AIDS may have parents radicals are produced in the who also have the disease, but these energy reactions. children acquired AIDS by viral infection, - Mitochondrial genes are not not by inheriting a mutation. wrapped in proteins. - Common symptoms may resemble those - Mitochondrial genes are not of an inherited condition, but be due to an “interrupted” by DNA sequences environmental situation. that do not encode protein. - For example, an underweight child who - A cell has many mitochondria and has frequent colds may show some signs each mitochondrion contains of cystic fibrosis, but may instead suffer several copies of the mitochondrial from malnutrition. genome. - Mitochondria with different alleles MITOCHONDRIAL GENES for the same gene can reside in the - Mitochondria are the cellular organelles same cell. that house the reactions that derive energy from nutrients. MITOCHONDRIAL DISEASES - Each of the hundreds to thousands of - Mitochondrial genes encode proteins that mitochondria in each human cell contains participate in protein synthesis and energy several copies of a “mini-chromosome” production. that carries just 37 genes. - Twenty-four of the 37 genes encode RNA molecules (22 transfer RNAs and 2 - Genes encoded in mitochondrial DNA ribosomal RNAs) that help assemble (mtDNA) act in the mitochondrion, but the proteins. organelle also requires the activities of - The other 13 mitochondrial genes encode certain genes from the nucleus. - The inheritance patterns and mutation proteins that function in cellular rates for mitochondrial genes differ from respiration, which is the process that uses those for genes in the nucleus. energy from digested nutrients to - Rather than being transmitted equally synthesize ATP, the biological energy molecule. from both parents, mitochondrial genes are maternally inherited. - They are passed only from an individual’s EXAMPLES mother because the sperm head, which - A class of diseases results from mutations enters an oocyte at fertilization, does not in mitochondrial genes. They are called include mitochondria, which are found in mitochondrial myopathies and have the sperm midsection, where they provide specific names, but news reports often energy for moving the tail. SOFIA BROSO PYN3 15 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM lump them together as “mitochondrial - A mitochondrial mutation may disrupt disease.” energy acquisition so greatly in an oocyte - Symptoms arise from tissues whose cells that it cannot survive. normally have many mitochondria, such as skeletal muscle, and include great fatigue, weak and flaccid muscles, and intolerance HETEROPLASMY to exercise. - The fact that a cell contains many - Skeletal muscle fibers appear “red and mitochondria makes possible a condition ragged” when stained and viewed under a called heteroplasmy, in which a mutation is light microscope, their abundant abnormal in some mitochondrial chromosomes, but mitochondria visible beneath the plasma not others. membrane. - At each cell division, the mitochondria are - Diseases considered to be mitochondrial distributed at random into daughter cells. may also result from mutations in nuclear - Over time, the chromosomes within a genes that encode proteins that are mitochondrion tend to be all wild type or all essential for mitochondrial function. mutant for any particular gene, but - A mutation in a mitochondrial gene that different mitochondria can have different alleles pre-dominating. encodes a tRNA or rRNA can be - As an oocyte matures, the number of devastating because it impairs the organelle’s general ability to manufacture mitochondria drops from about 100,000 to proteins. 100 or fewer. If the woman is heteroplasmic for a mutation, by chance, - Consider what happened to Lindzy, a once she can produce an oocyte that has active and articulate dental hygienist. mostly mitochondria that are wild type. - In her forties, Lindzy gradually began to - In this way, a woman who does not have a slow down at work. She heard a buzzing in mitochondrial disease, because the her ears and developed difficulty talking mitochondria bearing the mutation are and walking. either rare or not abundant in affected cell - Then her memory began to fade in and types, can nevertheless pass the out, she became lost easily in familiar associated condition to a child. places, and her conversation made no - Therefore, mitochondrial inheritance is sense. both complex and unpredictable. - Her condition worsened, and she developed diabetes, seizures, and - Heteroplasmy has several consequences pneumonia and became deaf and on phenotypes. demented. - Expressivity may vary widely among - She was finally diagnosed with MELAS, siblings, depending upon how many which stands for “mitochondrial myopathy mutation-bearing mitochondria were in the encephalopathy lactic acidosis syndrome.” oocyte that became each individual. - Her muscle cells had the telltale - Severity of symptoms reflects which red-ragged fibers. Lindzy died. Her son tissues have cells whose mitochondria and daughter will likely develop the bear the mutation. condition because they inherited her mitochondria. - This is the case for a family with Leigh syndrome, which affects the enzyme that - About 1 in 200 people has a mutation in a directly produces ATP. mitochondrial gene that could cause - Two boys died of the severe form of the disease. disease, because the brain regions that - However, mitochondrial diseases are rare, control movement rapidly degenerated. affecting about 1 in 6,500 people, - Another sibling was blind and had central apparently because of a weeding-out nervous system degeneration. process during egg formation. - Several relatives, however, suffered only mild impairment of their peripheral vision. SOFIA BROSO PYN3 16 PRINCIPLES OF GENETICS (LABORATORY) YEAR 2 | 1ST SEM - The more severely affected family energy production for embryonic members had more brain cells that development to complete. received the mutation-bearing - Often, severe heteroplasmic mitochondrial mitochondria. diseases do not produce symptoms until adulthood, because it takes many cell - The most severe mitochondrial illnesses divisions, and therefore years, for a cell to are heteroplasmic. This is presumably receive enough mitochondria bearing because homoplasmy—when all mutant alleles to cause symptoms. mitochondria bear the mutant allele—too severely impairs protein synthesis or SOFIA BROSO PYN3 17