* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Genetics - Aurora City School District
Polymorphism (biology) wikipedia , lookup
Minimal genome wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Genome evolution wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Genetic engineering wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Quantitative trait locus wikipedia , lookup
History of genetic engineering wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Gene expression programming wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Hybrid (biology) wikipedia , lookup
Genomic imprinting wikipedia , lookup
Designer baby wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Genome (book) wikipedia , lookup
Y chromosome wikipedia , lookup
Microevolution wikipedia , lookup
X-inactivation wikipedia , lookup
Topic 4 and 10 Why sex???? http://www.pbs.org/wgbh/nova/miracle/program. html Chromosomes Chromosomes are composed of DNA and protein (histone) Each body cell, called a somatic cell, is composed of 46 chromosomes (23 pairs). Each chromosome consists of two sister chromatids joined at the centromere. Chromosomes • Two chromosomes composing a pair are called homologous chromosomes (or homologues) because they both carry genes controlling the same inherited characteristics. • For example, if a gene that determines whether a person has freckles is located at a particular place, or locus, then the other chromosome of the homologous pair also has a gene for freckles at that locus – However, the two homologues may have different variations of the freckles genes (called alleles), perhaps one that promotes freckles and one that does not. Chromosomes • Sex chromosome – X and Y chromosomes – Determine the sex of an individual, and carry genes that perform other functions as well. – 23rd pair of chromosomes in humans • The two distinct chromosomes X and Y are important exception to the general pattern of homologous chromosomes. • Human females have a homologous pair of X chromosomes (XX), but males have one X and one Y chromosome (XY). – Only small parts of the X and Y are homologous; most of the genes carried on the X chromosome do not have counterparts on the tiny Y, and the Y chromosome has genes lacking on the X. Chromosomes The other 22 pairs of chromosomes are autosomes, or “body chromosomes”. For both autosomes and sex chromosomes, we inherit one chromosome of each pair form our mother and other from our father. *a key factor in the human life cycle and in the life cycles of all other species that reproduce sexually. Chromosomes Any cell with two homologous sets of chromosomes is called a diploid cell, and the total number of chromosomes is called the diploid number (abbreviated 2n) For humans, the diploid number is 46; that is 2n=46 Almost all human cells are diploid Chromosomes The exception are the egg and sperm cells, collectively known as gametes. Each gamete has a single set of chromosomes: 22 autosomes plus a single sex chromosome,either X or Y. A cell with a single chromosome set is called a haploid cell. For humans, the haploid number (abbreviated n) is 23; that is n=23 Chromosomes In humans, sexual intercourse allows a haploid sperm cell from the father to reach and fuse with a haploid egg cell of the mother in the process of fertilization. The resulting fertilized egg is called a zygote, which is now diploid. It has two haploid sets of chromosomes: one set from the mother and a homologous set from the father. The life cycle is completed as a sexually mature adult develops from the zygote. Mitotic cell division ensures that all somatic cells of the human body receive copies of all of the zygote’s 46 chromosomes. Chromosomes All sexual life cycles involve an alternation of diploid and haploid stages. Having haploid gametes keeps the chromosome number from doubling in each generation. Gametes are made by a special sort of cell division called meiosis, which occurs only in reproductive organs (ovaries and testes) Whereas mitosis produces daughter cells with the same numbers of chromosomes as the parent cell, meiosis reduces the chromosome number in half. Meiosis Meiosis Type of cell division that produces haploid gametes in diploid organisms. Many of the stages of meiosis closely resemble corresponding stages in mitosis. Meiosis, like mitosis, is preceded by the replication of chromosomes. However, this single replication is followed by two consecutive cell divisions, called Meiosis I and Meiosis II. These divisions result in four daughter cells, each with a single haploid set of chromosomes. Thus, meiosis produces daughter cells with only half as many chromosomes as the parent cell. Interphase Like mitosis, meiosis begins by interphase, during which the chromosomes duplicate. Occurs when the cell is between cell division Interphase stages: G1: Cells grow to mature size S: DNA is copied G2: Cell prepares for division At the end of interphase, each chromosomes consists of two genetically identical sister chromatids attached together. Chromosomes are not yet visible under the microscope; they are in a form called chromatin Prophase I Most complex phase of meiosis and typically occupies over 90% of the time required for meiotic cell division. Chromatin coils up so that individual chromosomes become visible A process called synapsis occurs, and homologous chromosomes, each composed of two sister chromatids, come together as pairs. Resulting structure, consisting of four chromatids, is called a tetrad. Chromatids of homologous chromosomes exchange segments in a process called crossing over: Rearranges genetic information, since homologues may be different from each other. This genetic shuffling makes an important contribution to the genetic variability resulting from sexual reproduction. Prophase I Prophase I As prophase I continues, the chromosomes condense further as the nucleoli disappear. Spindle fiber forms Nuclear envelope breaks down Metaphase I The chromosome tetrads are aligned on the metaphase plate, midway between the two poles of the spindle. Each chromosome is condensed and thick, with its sister chromatids still attached at their centromeres Spindle microtubules are attached at centromeres. In each tetrad, the homologous chromosomes are held together at sites of crossing over. Within each tetrad, the spindle microtubules attached to one of the homologous chromosomes from one pole of the cell, and the microtubules attached to the other homologous chrome come from the opposite pole Getting set up to separate the homologous chromsomes! Metaphase I Anaphase I Sister chromatids remain attached, however, the tetrads split up . The sister chromatids move to opposite poles The cells are now containing half of the genetic information from the original parent cell and are thus considered HAPLOID! Anaphase I Telophase I and Cytokinesis Chromosomes arrive at the poles of the cell Each pole of the cell has a haploid chromosome set, although each chromosome is still in duplicate form at this point= each chromosome still consists of two sister chromatids. Cytokinesis occurs along with telophase I and two haploid daughter cells are formed. Telophase I Before Meiosis II… In some organisms, the chromosomes uncoil and the nuclear envelope re-forms, and there is an interphase before meiosis II begins. IN other species, daughter cells produced during the first meiotic division immediately begin preparation for the second meiotic division. In either case, NO chromosome duplication occurs between telophase I and the onset of meiosis II. Meiosis II In organisms having an interphase after meiosis I, the chromosomes condense again and the nuclear envelope breaks down during prophase II. In any case, meiosis II is essentially the same as mitosis. The key difference is that meiosis II starts with a haploid cell. Prophase II A spindle forms and moves the chromosomes toward the middle of the cell. Metaphase II Chromosomes are aligned on the metaphase plate as they are in mitosis, with the centromeres of the sister chromatids pointing towards opposite poles. Anaphase II centromeres of sister chromatids finally separate the sister chromatids of each pair, now individual chromosomes, move toward opposite poles of the cell. Telophase II Nuclei form at the cell poles, and cytokinesis occurs at the same time. There are now four daughter cells, each with the haploid number of (single) chromosomes. Meiosis Animation http://www.sumanasinc.com/webcontent/animations /content/meiosis.html Mitosis vs. Meiosis Mitosis Provides growth, tissue repair, and asexual reproduction Produces daughter cells genetically identical to the parent cell Involves one division of the nucleus, and is usually accompanied by cytokinesis, producing two diploid daughter cells. Meiosis Need for sexual reproduction Entails two nuclear and cytoplasmic divisions Yields four haploid daughter cells, with one member of each homologous chromosome pair. Form tetrads; crossing over occurs. Meiosis: Genetic Variation We’ve discussed how mutations lead to genetic variation. Also, The arrangement of homologous chromosomes pairs at metaphase of meiosis I affects the resulting gametes. The orientation of homologous pairs in the center of the cell is random; thus producing gametes with random chromosomes For any species, the total number of combinations of chromosomes that meiosis can package into gametes is 2n, where n is the haploid number. For a human, 223, or about 8 million possible chromosome combinations This means that each gamete you produce contains one of roughly 8 million possible combinations of chromosomes inherited from your mother and father. Meiosis: Genetic Variation Possibility when a gamete from one individual unites with a gamete from another individual in fertilization: In humans, the random fusion of a single sperm wit a single ovum during fertilization will produce a zygote with any of 64 trillion (8 million x 8 million) combinations of chromosomes! Meiosis: Genetic Variation Homologous chromosomes Bear two different kinds of genetic information for the same characterisitic The key to what really makes gametes—and therefore offspring--different Meiosis: Genetic Variation Crossing Over: An exchange of corresponding segments between two homologous chromosomes. Occurs during prophase I of meiosis. Chromosomes are a tetrad—four chromatids, with each pair of sister chromatids joined at their centromeres. Each gene on each homologue is aligned precisely with the corresponding gene on the other homologue Sites of crossing over appear as X-shaped regions; each is called a chiasma. place where two homologous chromatids are attached to each other. Can produce new combinations of genes= genetic recombination! Meiosis: Genetic Variation Crossing over: 1. The DNA molecules of two nonsister chromatids—one maternal and one paternal—break at the same place. 2. Immediately, the two broken chromatids join together in a new way . In effect, the two homologous segments trade places, or cross over, producing hybrid chromosomes with new combinations of maternal and paternal genes. Called “recombinants” 3. When the homologous chromosomes separate in anaphase I, each contains a new segment originating form its homologues. 4. Finally, in meiosis II, the sister chromatids separate, each going to a different gamete. **In meiosis in humans, an average of one to three crossover events occur per chromosome pair. Crossing Over Meiosis: Genetic Variation In summary, there are three sources of genetic variability, besides mutations, in sexually reproducing organisms: 1. crossing over during prophase I 2.independent orientation of chromosomes at metaphase 1 3.random fertilization Karyotypes The term karyotype refers to the chromosome complement of a cell or a whole organism. A karyotype is an ordered display of magnified images of an individual’s chromosomes arranged in pairs, starting with the longest. In particular, it shows the number, size, and shape of the chromosomes as seen during metaphase of mitosis. Chromosome numbers vary considerably among organisms and may differ between closely related species. Karyotypes Karyotypes are prepared from the nuclei of cultured white blood cells that are ‘frozen’ at the metaphase stage of mitosis. Shows the chromosomes condensed and doubled A photograph of the chromosomes is then cut up and the chromosomes are rearranged on a grid so that the homologous pairs are placed together. Homologous pairs are identified by their general shape, length, and the pattern of banding produced by a special staining technique. Karyotypes Male karyotype Has 44 autosomes, a single X chromosome, and a Y chromosome (written as 44 + XY) Female karyotype Shows two X chromosomes (written as 44 + XX) Karyotype- Normal Karyotype- Down Syndrome Down Syndrome Trisomy 21; named after John Langdon Down, who characterized the syndrome in 1866 47 chromosomes total; there are three number 21 chromsomes In most cases, a human embryo with an abnormal number of chromosomes is spontaneously aborted (miscarried) long before birth. Some chromosome abnormalities upset the genetic balance less drastically, and individuals carrying them can survive. Down Syndrome Trisomy 21 is the most common chromosome number abnormality. Affects about one out of every 700 children born, and is the most common serious birth defect in the US Symptoms include characteristic facial features, notably a round face, a skin fold at the inner corner of the eye, a flattened nose bridge small, irregular teeth, as well as short stature heart defects, and susceptibility to respiratory infections, leukemia, and Alzheimer’s disease. Exhibit varying degrees of mental retardation. Some live to middle age or beyond, and many are socially adept and able to hold jobs. Most are sexually underdeveloped and sterile A few women have had children, however, half of their eggs will have the extra chromosome 21, so there is a 50% chance that she will transmit the syndrome to her child. Down Syndrome Down Syndrome incidence: The incidence of Down Syndrome in the offspring of normal parents increases remarkedly with the age of the mother. Strikes less than 0.05% of children (fewer than one in 2,000) born to women under age 30. Risk climbs to 1.25% for mothers in their early 30s and is even higher for older mothers. Because of this relatively high risk, pregnant women over 35 are candidates for fetal testing for trisomy 21 and other chromosomal abnormalities. Maternal age and incidence of Down Syndrome Errors in Meiosis Nondisjunction Members of a chromosome fail to separate. Can lead to an abnormal chromosome number in any sexually reproducing diploid organism. For example, if there is nondisjunction affecting human chromosome 21 during meiosis I, half the resulting gametes will carry an extra chromosome 21. Then, if one of these gametes unites with a normal gamete, trisomy 21 (Down Syndrome) will result. Errors is Meiosis Two ways that nondisjunction can occur: 1.a pair of homologous chromosomes does not separate during Meiosis I. Two of the gametes produced will n + 1(abnormal), and two will be n- 1 (abnormal). 2. meiosis I is normal, but one pair of sister chromatids fails to separate during meiosis II. Two of the resulting gametes are n + 1 and n-1 (abnormal) and two will be n (normal) Abnormal gametes that get fertilized, will result in a zygote with an extra chromosome. Mitosis will then transmit the anomaly to all embryonic cells, causing some syndrome linked to abnormal genes. Errors in Meiosis What causes nondisjunction? We do not yet know the answer, nor do we fully understand why offspring with trisomy 21 are more likely to by born as a woman ages. We do know, however, that meiosis begins in a woman’s ovaries before she is born but is not completed until years later, at the time of an ovulation. Because only one egg usually matures each month, a cell might remain arrested in the mid-meiosis state for decades. Some research points to an age-dependent error in one of the checkpoints that coordinates the process of meiosis. Errors in Meiosis Nondisjunction can also occur in sex chromosomes. For example, Klinefelter’s Syndrome : males have an extra X chromosome, making him XXY occurs approximately 1 out of every 2,000 live births Have male sex organs, but the testes are abnormally small and the individual is sterile. Often includes breast enlargement and other female body characteristics. Person is usually of normal intelligence Errors in Meiosis Nondisjunction in sex chromosomes: Turner Syndrome Females who are lacking an X chromosome= XO, the O indicates the absence of a second chromosome Characteristic appearance include short stature, and often a web of skin extending between the neck and the shoulders Sterile; their sex organs do not fully mature at adolescence If left untreated, girls will have poorly developed breasts and other secondary sexual characteristics. Normal intelligence *Sole known case where having 45 chromosomes is not fatal. Errors in Meiosis Nondisjunction in sex chromosomes: Males with XYY and females with XXX are normal. Errors in Meiosis Abnormalities in chromosome structure: Breakage of a chromosome can lead to a variety of rearrangements affecting the genes of that chromosome: 1. deletion: if a fragment of a chromosome is lost. Usually cause serious physical and mental problems. Deletion of chromosome 5 causes cri du chat syndrome: child is mentally retarded, has a small head with unusual facial features, and has a cry that sounds like the mewing of a distressed cats. Usually die in infancy or early childhood. 2.duplication: if a fragment from one chromosome joins to a sister chromatid or homologous chromosome. 3.inversion: if a fragment reattaches to the original chromosome but in the reverse direction. Less likely than deletions or duplications to produce harmful effects, because all genes are still present in normal number Errors in Meiosis Abnormalities in chromosome structure: Translocation The attachment of a chromosomal fragment to a nonhomologous chromosome. May or may not be harmful For example, chromosomal translocation in a somatic cell in the bone marrow is associated with chronic myelogenous leukemia (CML), which is the most common type of leukemia, the cancer that affects the cells that give rise to white blood cells (leukocytes) Part of chromosome 22 has switched with a small fragment of chromosome 9. The chromosome with the cancer-causing gene is called the “Philadelphia chromosome”, after the city where it was discovered. Errors in Meiosis Gregor Mendel Gregor Mendel Background: Deduced the fundamental principles of genetics by breeding garden peas. Known as the “Father of Genetics” Was a monk that lived and worked in an abbey in Austria. In a paper in 1866, Mendel correctly argued that parents pass on to their offspring discrete heritable factors. In his paper, he stressed that the heritable factors (today called genes) retain their individuality generation after generation. Gregor Mendel Experiments: Chose to study garden peas because he was familiar with them from his rural upbringing, they were easy to grow, and they came in many readily distinguishable varieties. Also, he was able to exercise strict control over pea plant matings. Due to their anatomical nature (petals of pea flower almost completely enclose the stamen and carpel), pea plants usually self-fertilize in nature. That is, sperm-carrying pollen grains released from the stamens land on the egg-containing carpel of the same flower. He used a small bag to cover the flower to ensure selffertilization. Gregor Mendel Experiments (continued) He was also able to ensure cross-fertilization Fertilization of one plant by pollen from a different plant. Through his methods, Mendel could always be sure of the parentage of new plants He chose seven characteristics, that occur in two distinct forms ,to study: Flower color (purple, white) Flower position (axial, terminal) Seed color (yellow, green) Seed shape (round, wrinkled) Pod shape (inflated, constricted) Pod color (green, yellow) Stem length (tall, dwarf) Gregor Mendel Experiments (continued): Mendel worked with his plants until he was sure he had true- breeding varieties. For instance, he identified a purple-flowered variety that, when self-fertilized, produced offspring that all had purple flowers. He then asked, What offspring would result if plants with purple flowers and plants with white flowers were cross-fertilized? The offspring of two different varieties are called hybrids, and the cross-fertilization itself is referred to as a hybridization, or simply a cross. The true-breeding parental plants are called the P generation ( P for parental). The offspring of the P generation are called the F1 generation (F for filial, the Latin word “son”) When the F1 self-fertilize or fertilize with each other, their offspring are called the F2 generation. Gregor Mendel Mendel performed many experiments in which he tracked the inheritance of characteristics that occur in two forms, such as flower color. Monohybrid cross: When you’re looking only at one trait (ex, flower color) Mendel performed a monohybrid cross between a pea plant with purple flowers and one with white flowers. The F1 offspring all had purple flowers (not a lighter purple, has predicted by a “blending” hypothesis.) Was the white gene lost? By mating the F1 plants, Mendel found the answer to be NO! Out of 929 F2 plants, Mendel found that 705 (about ¾) had purple flowers and 224 (about ¼) had white flowers, a ratio of about three plants with purple flowers to one with white flowers in the F2 generation (3:1) The heritable factor for white flowers did not disappear in the F1 plants, but the purple-flower factor was the only one affecting the F1 flower color. The F1 plants must have carried two factors for the flower-color characteristic, one for purple and one for white. Gregor Mendel Gregor Mendel Mendel observed these same patterns of inheritance for six other pea plant characteristics. From these results, he developed four hypotheses, which we will describe using modern terminology (such as “gene” instead of “heritable factor”): Gregor Mendel Hypothesis 1: There are alternative forms of genes that account for variations in inherited characteristics. For example, the gene for flower color in pea plants exists in two forms, one for purple and the other for white. The alternative versions of a gene are now called alleles. Gregor Mendel Hypothesis 2: For each characteristic, an organism inherits two alleles, one from each parent. These alleles may be the same ore different. An organism that has two identical alleles for a gene is said to be homozygous for that gene (and is called a homozygote). An organism that has two different alleles for a gene is said to be heterozygous for that gene (and is called a heterozygote) Gregor Mendel Hypothesis 3: If the two alleles of an inherited pair differ, then one determines the organism’s appearance is called the dominant allele; the other has no noticeable effect on the organism’s appearance and is called the recessive allele. We use upper-case letters to represent dominant alleles and lowercase letters to represent recessive alleles. Gregor Mendel Hypothesis 4: A sperm or egg carries only one allele for each inherited trait because allele pairs separate (segregate) from each other during the production of gametes. This statement is now known as the law of segregation. When sperm and egg unite at fertilization, each contributes its allele, restoring the paired condition in the offspring. Gregor Mendel The right hand side of the diagram on the previous slide explains the results of Mendel’s experiment. In this example, P represents the dominant allele (for purple flowers) and p represents the recessive allele (for white flowers). At the top, you see the alleles carried by the parental plants both were true-breeding. Mendel proposed that one parent had two alleles for purple flowers (PP) and the other had two alleles for white flowers (pp) Consistent with hypothesis 4, the gametes of Mendel’s parental plants each carried one allele; thus, the parental gametes in Figure 9.3B are either P or p. As a result of fertilization, the F1 hybrids each inherited one allele for purple flowers and one for white. Hypothesis 3 explains why all of the F1 hybrids are (Pp) had purple flowers; the dominant P allele has its full effect in the heterozygote, while the recessive p allele had no effect on flower color. Gregor Mendel The right hand side of the diagram on the previous slide explains the results of Mendel’s experiment (continued…) Mendel’s hypotheses also explain the 3:1 ratio in the F2 generation; because the F1 hybrids are Pp, they make gametes P and p in equal numbers. You can see the possible gamete combinations using a Punnett square. Used to make predictions about the possible phenotypes and genotypes of offspring. Gregor Mendel Genotype vs. Phenotype Phenotype For example, purple or white flowers. Term used to describe an organism’s appearance, or expressed physical traits. Phenotypic ratio- ratio of the phenotypes of the offspring. Example, the ratio of purple flowers to white flowers is 3:1 Genotype For example, PP, Pp, or pp. Term used to describe an organism’s genetic makeup. Genotypic ratio- ratio of the genotypes of the offspring. Example, the 1:2:1 is the ratio of PP, Pp, pp Homologous Chromosomes Remember, two homologous chromosomes may bear either the same alleles or different ones. Thus, we see the connection between Mendel’s laws and homologous chromosomes: Alleles (alternate forms) of a gene reside at the same locus on homologous chromosomes. Test Cross Test Cross: a mating between an individual of unknown genotype and a homozygous recessive individual. Mendel used testcrosses to determine whether he had true-breeding varieties of plants. Continues to be an important tool of geneticists for determining genotypes. Not so simple… Although Mendel’s laws are valid for all sexually reproducing organisms, they stop short of explaining some patterns of genetic inheritance. In fact, for most sexually reproducing organisms, cases where Mendel’s laws can strictly account for the pattern of inheritance are relatively rare. More often, the inheritance patterns are more complex… Incomplete dominance Complete dominance The dominant allele had the same phenotypic whether present in one or two copies. Incomplete dominance The F1 hybrids have an appearance in between the phenotypes of the two parental varieties. Incomplete Dominance For example, red snapdragons crossed with white snapdragons produced hybrid flowers in the F1 with pink flowers. This third phenotype results from flowers of the heterozygote having less pigment than the red homozygotes. The F2 generation would then have a 1:2:1 ratio of red, pink, white. Incomplete dominance In humans, an example involves the condition hypercholestrolemia, dangerously high levels of cholesterol in the blood, caused by a recessive allele(h), due to a lack of LDL receptors. hh individuals have about 5 times the normal amount of blood cholesterol and may have heart attacks as early as age 2. Normal individuals are HH. Heterozygotes have blood cholesterol about twice normal. Usually prone to atherosclerosis, the blockage of arteries by cholesterol buildup in artery walls, and they may have heart attacks from blocked heart arteries by their mid-30s. Codominance Both alleles are expressed in the heterozygous individual Different from incomplete dominance, which is the expression of one intermediate trait Can be seen in blood type Codominance The ABO blood group phenotype in humans involves three alleles of a single gene. These three alleles, in various combinations, produce four phenotypes: a person’s blood group may be either O, A, B, or AB. These letters refer to two carbohydrates, designated A and B, that may be found on the surface of red blood cells. A person’s red blood cells may have carbohydrate A (type A blood), carbohydrate B (type B), both (type AB), or neither (type O). Codominance Matching compatible blood groups is critical for safe blood transfusions. If a donor’s blood cells have carbohydrate (A or B) that is foreign to the recipient, then the recipient’s immune system produces blood proteins called antibodies that bind specifically to the foreign carbohydrates and cause donor blood cells to clump together, potentially killing the recipient. Codominance Four blood groups result from various combinations of the three different alleles, symbolized as IA, IB, and i. Each person inherits one of these alleles from each parent. IA and IB are dominant to the i allele, but are codominant to each other = both alleles are expressed in the heterozygote IAIB , who have the blood type AB There are six possible genotypes: IAIA and IAi= A IBIB and IBi= B IAIB= AB ii = O Dihybrid cross Dihybrid cross: Results from a mating of parental varieties differing in two characteristics. For example: Mendel crossed homozygous round yellow seeds (RRYY) with plants having wrinkled green seeds (rryy). All of the offspring in the F1 generation had round yellow seeds; which raised the question: are the two characteristics transmitted from parent to offspring as a package, or was each characteristic inherited independently of the other? The question was answered when Mendel allowed fertilization to occur among the F1 plants the offspring supported the idea that the two seed characteristics segregated independently. Offspring had nine different genotypes, and four different phenotypes with 9:3:3:1 ratio. Dihybrid Cross Mendel’s results supported the hypothesis that each pair of alleles segregates independently of the other pairs of alleles during gamete formation Mendel’s Law of Independent Assortment Pleiotropy Most genes influence multiple characteristics, a property called pleiotropy. An example of pleiotropy in humans is sickle-cell disease Refer to p. 168 Polygenic Inheritance Polygenic inheritance is the additive effects of two or more genes on a single phenotypic characteristic Examples include human skin color and height Different then pleiotropy, in which a single gene affects several characteristics Environmental affects Many characteristics result from a combination of heredity and environment. For example, in humans nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests. It is becoming clear that human phenotypes—such as risk of heart disease and cancer and susceptibility to alcoholism and schizophrenia—are influenced by both genes and environment. Simply spending time with identical twins will convince anyone that environment, and not just genes, affect a person’s traits. However, only genetic influences are inherited…cannot pass on environmental influences to future generations! Chromosome Theory of Inheritance The chromosome theory states that genes occupy specific loci (positions) on chromosomes and it is the chromosomes that undergo segregation and independent assortment during meiosis. Thus, it is the behavior of chromosomes during meiosis and fertilization that accounts for inheritance patterns. Linked genes Genes located close together on the same chromosome tend to be inherited together and are called linked genes. Linked genes generally do not follow Mendel’s law of independent assortment. Refer to figure 9.19 in book Crossing over As we saw in meiosis, crossing over between homologous chromosomes produces new combinations of alleles in gametes Forms recombinant gametes Sex Chromosomes Sex chromosomes, designated X and Y, determine an individual’s sex. XX individuals ar e female, and XY individuals are male Human males and females both have 44 autosomes (nonsex chromosomes) As a result of chromosome segregation during meiosis, each gamete contains one sex chromosome and a haploid set of autosomes (22). All eggs contain a single X chromosome; sperm either contain an X or Y An offspring’s sex is determined by whether the sperm cell that fertilizes the egg bears an X or Y Sex Chromosomes The genetic basis of sex determination in humans is not yet completely understood, but one gene on the Y chromosome plays a crucial role. This gene is called SRY (sex-determing region of Y) and triggers testis development. In the absence of SRY, an individual develops ovaries rather than testes. SRY codes for proteins that regulate other genes on the Y chromosome, which in turn produce proteins necessary for testis development. Sex-linked genes Besides bearing genes that determine sex, the sex chromosomes also contain genes for characteristics unrelated to femaleness and maleness. Sex-linked genes are genes located on either sex chromosomes, although in humans the term has historically referred specifically to a gene on the X chromosome. ***Be careful not to confuse the term sexlinked gene with the term linked genes!!!*** Refer to figure 9.23A-D on p. 176 Pedigrees Pedigree is a family tree used to study how particular human traits are inherited. It is analyzed using logic and the Mendelian laws Goals of Pedigree Analysis 1. Determine the mode of inheritance: dominant, or recessive, sex-linked or autosomal 2. Determine the probability of an affected offspring for a given cross. Basic symbols More Symbols Dominant or Recessive? Is it a dominant pedigree or a recessive pedigree? 1. If two affected people have an unaffected child, it must be a dominant pedigree: D is the dominant mutant allele and d is the recessive wild type allele. Both parents are Dd and the normal child is dd. 2. If two unaffected people have an affected child, it is a recessive pedigree: R is the dominant wild type allele and r is the recessive mutant allele. Both parents are Rr and the affected child is rr. 3. If every affected person has an affected parent it is a dominant pedigree. Dominant Autosomal Pedigree I 2 1 II 1 2 3 4 5 6 III 1 2 3 4 5 6 7 8 9 10 Assigning Genotypes for Dominant Pedigrees 1. All unaffected are dd. 2. Affected children of an affected parent and an unaffected parent must be heterozygous Dd, because they inherited a d allele from the unaffected parent. 3. The affected parents of an unaffected child must be heterozygotes Dd, since they both passed a d allele to their child. (also called carriers) 4. If both parents are heterozygous Dd x Dd, their affected offspring have a 2/3 chance of being Dd and a 1/3 chance of being DD. Recessive Autosomal Pedigree Assigning Genotypes for Recessive Pedigrees 1. all affected are rr. 2. If an affected person (rr) mates with an unaffected person, any unaffected offspring must be Rr heterozygotes, because they got a r allele from their affected parent. 3. If two unaffected mate and have an affected child, both parents must be Rr heterozygotes. 4. Recessive outsider rule: outsiders are those whose parents are unknown. In a recessive autosomal pedigree, unaffected outsiders are assumed to be RR, homozygous normal. 5. Children of RR x Rr have a 1/2 chance of being RR and a 1/2 chance of being Rr. Note that any siblings who have an rr child must be Rr. 6. Unaffected children of Rr x Rr have a 2/3 chance of being Rr and a 1/3 chance of being RR. Outsider Rules In any pedigree there are people whose parents are unknown. These people are called “outsiders”, and we need to make some assumptions about their genotypes. Sometimes the assumptions are proved wrong when the outsiders have children. Also, a given problem might specify the genotype of an outsider. Outsider rule for dominant pedigrees: affected outsiders are assumed to be heterozygotes. (or carriers) Outsider rule for recessive pedigrees: unaffected (normal) outsiders are assumed to be homozygotes. Both of these rules are derived from the observation that mutant alleles are rare. Autosomal Dominant All unaffected individuals are homozygous for the normal recessive allele. AutosomalDominant Look for: Trait in every generation Once leaves the pedigree does not return Every person with the trait must have a parent with the trait Males and females equally affected Autosomal Dominant Autosomal Dominant Autosomal Recessive The recessive gene is located on 1 of the autosomes Letters used are lower case ie bb Unaffected parents (heterozygous) can produce affected offspring (if they get both recessive genes ie homozygous) Inherited by both males and females Can skip generations If both parents have the trait then all offspring will also have the trait. The parents are both homozygous. E.g. cystic fibrosis, sickle cell anaemia, thalassemia Autosomal Recessive Look for: Skips in generation Unaffected parents can have affected children Affected person must be homozygous Males and females affected equally Autosomal Recessive AutosomalRecessive Sex Linked Inheritance Genes are carried on the sex chromosomes (X or Y) Sex-linked notation XBXB normal female XBXb carrier female XbXb affected female XBY normal male XbY affected male Sex-linked dominant Mothers pass their X’s to both sons and daughters If the mother has an X- linked dominant trait and is homozygous (XAXA) all children will be affected If Mother heterozygous (XAXa) 50% chance of each child being affected Fathers pass their X to daughters only. Affected males pass to all daughters and none of their sons Genotype= XAY Normal outsider rule for dominant pedigrees for females, but for sexlinked traits remember that males are hemizygous and express whichever gene is on their X. XD = dominant mutant allele Xd = recessive normal allele E.g. dwarfism, rickets, brown teeth enamel. Sex-Linked Dominant Look for: More males being affected Affected males passing onto all daughter (dominant) and none of his sons Every affected person must have an affected parent Sex-Linked Recessive males get their X from their mother fathers pass their X to daughters only females express it only if they get a copy from both parents. Females can only inherit if the father is affected and mother is a carrier (hetero) or affected (homo) expressed in males if present More males than females affected (males inherit X from mother) recessive in females An affected female will pass the trait to all her sons Daughters will be carriers if father is not affected Outsider rule for recessives (only affects females in sex-linked situations): normal outsiders are assumed to be homozygous. Males cannot be carriers (only have 1 X so either affected or not) Can skip generations E.g. colour blindness, haemophilia, Duchene muscular dystrophy Sex Linked Recessive Look for: More males being affected Affected female will pass onto all her sons Affected male will pass to daughters who will be a carrier (unless mother also affected) Unaffected father and carrier mother can produce affected sons Sex-linked recessive Sex-linked recessive