* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download H 2
Site-specific recombinase technology wikipedia , lookup
Public health genomics wikipedia , lookup
History of genetic engineering wikipedia , lookup
Point mutation wikipedia , lookup
Population genetics wikipedia , lookup
Genome evolution wikipedia , lookup
Ridge (biology) wikipedia , lookup
Minimal genome wikipedia , lookup
Medical genetics wikipedia , lookup
Genetic drift wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Gene expression profiling wikipedia , lookup
Gene expression programming wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Genomic imprinting wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
Y chromosome wikipedia , lookup
Genome (book) wikipedia , lookup
Neocentromere wikipedia , lookup
Bio 211 d15 Quiz on Mendelian genetics What are the two laws of Mendel What aspect of meiosis is responsible for these outcomes? Do Mendel’s rules always apply? Well, sometimes – as long as: Each trait is completely controlled by a single gene Only two possible alleles of each gene exist One allele is completely dominant to the other, recessive, allele Fly lab with Mendelian traits! Follow inheritance of several traits and see if they are Mendelian 1. Choose individual traits and follow single trait – monohybrid crosses for Wings: curved or dumpy Eyes: sepia, eyeless, or lobe 2. Choose two that are Mendelian and follow dihybrid cross Wing/eye combo above Body and bristles combo Body: either black or ebony Bristles: either spineless or shaven 3. Discuss non-Mendelian genetics Incomplete dominance Sex-linkage Polygenic inheritance 4. Predict the outcome Of the wing cross if it were sex-linked Of the eye cross if it were incompletely dominant Do Mendel’s rules always apply? Well, sometimes – as long as: Each trait is completely controlled by a single gene Only two possible alleles of each gene exist One allele is completely dominant to the other, recessive, allele However: Many traits are influenced in more varied or subtle ways So today… the million interesting exceptions Sex linkage Incomplete dominance Multiple alleles Co-dominance Polygenic inheritance Human genetic disorders!!! And so much more… Incomplete dominance • phenotype of the heterozygotes is intermediate between the phenotypes of the homozygotes – In the genes studied by Mendel, one allele was dominant over the other, which was recessive – Some alleles, however, are only partially dominant over others – When the heterozygous phenotype is intermediate between the two homozygous phenotypes, the pattern of inheritance is called incomplete dominance – Human hair texture is influenced by a gene with two incompletely dominant alleles, H1 and H2 • • • • • A person with two copies of the H1 allele has curly hair Homozygotes for the H2 allele have straight hair Heterozygotes (H1H2) have wavy hair In this case, can you tell genotype based on the phenotype? If two wavy-haired people marry, their children could have any of the three hair types: curly (H1H1), wavy (H1H2), or straight (H2H2) • In what ratios? – What is your hair phenotype? Predict your HH genotype. Figure 10-13 Incomplete dominance mother H1H2 H1 H1H2 H2 H1 sperm father eggs H1H1 H1H2 H1H2 H2H2 H2 Do all genes have only two alleles? • A single gene may have multiple alleles – An individual may have at most ___different gene alleles – A species may have multiple alleles for a given characteristic – Human blood type is an example of multiple alleles of a single gene – Human blood group genes produce blood types A, B, AB, and O • There are ____ alleles in this system: A, B, and O • So what are the genotypes and what are the phenotypes? How does blood type work? • Alleles A and B code for enzymes that add different sugar molecules to the ends of glycoproteins that protrude from red blood cells • Allele O codes for a nonfunctional enzyme that doesn’t add any sugar molecules • Blood types A, B, AB, and O arise as a result of the actions of these alleles • Why does this cause a phenotype?? What are the genetic relationships • People with AA or AO genotypes have blood type A – A is dominant to O, which is recessive • People with BB or BO genotypes have blood type B – B is dominant to O, which is recessive • People with OO genotypes have blood type O – Just like the white-flowered plants are pp • People with AB genotypes have blood type AB – So what does that mean about A and B – are they dominant? Recessive? – They are co-dominant to each other! What do these genes actually DO?? • Alleles A and B code for enzymes – If A is present, enzyme A makes one kind of glycoprotein – If B is present, a different glycoprotein is made – In AB, both glycoproteins are present on the RBC surface • O individuals lack the enzyme – OO individuals have no enzyme, hence no A or B glycoproteins The consequence of blood type • We make antibodies to the glycoproteins we LACK – People with type A blood make ___antibodies; people with type B blood make ____ antibodies – People with type O blood make ___ and _____antibodies; type AB blood groups make _____ antibodies – The antibodies cause red blood cells that bear foreign glycoproteins to clump together and rupture – The presence of such antibodies dictates that blood type must be determined and matched carefully before a blood transfusion is made The consequence of blood type • We make antibodies to the glycoproteins we LACK – People with type A blood make B antibodies; people with type B blood make A antibodies – People with type O blood make both type A and type B antibodies; type AB blood groups make no antibodies – The antibodies cause red blood cells that bear foreign glycoproteins to clump together and rupture – The presence of such antibodies dictates that blood type must be determined and matched carefully before a blood transfusion is made What is the best donor or recipient to be? • Type O blood, lacking any sugars, is not attacked by antibodies in A, B, or AB blood, so is transfused safely to all – Type O blood is called the universal donor – The A and B antibodies in type O blood become too dilute to cause problems in the recipient of transfused type O blood – Are O type good recipients? – Because people with type O blood produce both A and B antibodies, they can receive blood only from other type O donors • Their antibodies would attack any donated blood cells bearing A or B glycoproteins • Best recipient would be ? • AB (no antibodies to anything) Table 10-1 Are all traits determined by just one gene? • Many traits are influenced by several genes – Some characteristics show a range of continuous phenotypes instead of discrete, defined phenotypes – Such as? • height, skin color, and body build in humans • These traits are influenced by interactions among two or more genes through a process called polygenic inheritance Polygenic inheritance • Traits affected by polygenic inheritance are often strongly affected by the environment, further blurring the differences among phenotypes • Human skin color is controlled by at least three genes, each with pairs of incompletely dominant alleles • According to research, human height is controlled by at least 180 genes Figure 10-14 Polygenic inheritance of skin color in humans Humans show a wide range of skin tones, from almost white to very dark brown Some genes affect more than one thing • Some genes have multiple effects on phenotype – Alleles that have multiple phenotypic effects are said to have pleiotropy because they influence more than one phenotype – The SRY gene on the Y chromosome in male humans encodes a protein that activates other genes • The SRY gene stimulates development of gonads into testes, which in turn stimulates development of the prostate, seminal vesicles, penis, and scrotum Environmental effects • The environment can profoundly affect phenotype • Newborn Siamese cats demonstrate the effect of environment on phenotype – A Siamese cat has the genotype for dark fur all over its body – However, the enzyme that produces the dark pigment is inactive at temperatures above 93F (34C) – When kittens are in the warmth of their mother’s uterus, the enzyme is inactive and they are born with pale fur everywhere – After birth, the ears, nose, paws, and tail become cooler than the rest of the body, and dark pigment is produced there in the pattern characteristic of the breed Figure 10-16 Environmental influence on phenotype Some genes are linked • Genes on the same chromosome tend to be inherited together – Mendel’s law of independent assortment works only for genes whose loci are on different pairs of homologous chromosomes – Alleles that are on the same chromosome do not line up independently of one another on the metaphase plate and are not separated at anaphase I – Genes on the same chromosome tend to be inherited together, a phenomenon called gene linkage For example • flower color and pollen in sweet peas are linked –Meaning: these loci are on the same chromosome –Purple flower color is dominant to red; long pollen shape is dominant to round –Let P = purple flowers and p = red flowers –Let L = long pollen shape and l = round shape – What are the expected gametes from parent PpLl, where P is linked with L and p is linked with l ? – Independent assortment would yield gametes in a genetic proportion of 1/4 PL, 1/4 Pl, 1/4 pL, 1/4 pl – Instead, the gametes are mostly PL and pl Figure 10-17 Linked genes on homologous chromosomes in the sweet pea flower-color gene pollen-shape gene purple allele, P long allele, L red allele, p round allele, l Can we separate normally co-inherited alleles? • Crossing over creates new combinations of linked alleles – Genes on the same chromosome do not always stay together – Crossing over involves the exchange of DNA between chromatids of paired homologous chromosomes in synapsis – The farther apart two linked gene loci are on a chromosome, the more likely crossing over is to occur between them – Crossing over occurs so often between loci far apart on a chromosome that they appear to assort independently – When does the pairing and swapping happen? – Crossing over, or genetic recombination, in prophase I of meiosis creates new gene combinations Figure 10-18a Duplicated chromosomes in prophase of meiosis I flower-color gene pollen-shape gene sister chromatids purple allele, P long allele, L homologous chromosomes (duplicated) at meiosis I sister chromatids red allele, p round allele, l Duplicated chromosomes in prophase of meiosis I Figure 10-18b Crossing over during prophase I P L P L p l p l Crossing over during prophase I Figure 10-18c Homologous chromosomes separate at anaphase I recombined chromatids P L p L P l p l unchanged chromatids Homologous chromosomes separate at anaphase I Figure 10-18d Unchanged and recombined chromosomes after meiosis II recombined chromosomes P L p L P l p l unchanged chromosomes Unchanged and recombined chromosomes after meiosis II sex chromosomes! Animals have a set of sex chromosomes that dictate gender In mammals, females have two X chromosomes In mammals, males have an X chromosome and a Y chromosome • The Y chromosome is much smaller than the X chromosome A small section of the X and Y chromosomes is homologous, allowing them to pair in prophase I and segregate during meiosis The rest of the (non-sex) chromosomes occur in identical pairs and are called autosomes Figure 10-19 Human sex chromosomes Y chromosome X chromosome Mammals – sex is determined by sperm – For organisms in which males are XY and females are XX, the sex chromosome carried by the sperm determines the sex of the offspring • During sperm formation, each sperm receives either the X or the Y chromosome, along with a copy of each of the autosomes • Because the female has only X sex chromosomes, the unfertilized egg must have an X chromosome • If the egg is fertilized by a sperm with a Y chromosome, a male results; if fertilized by an X-bearing sperm, a female is produced Figure 10-20 Sex determination in mammals female parent X1 X2 eggs X1 X1 male parent Y X2 Xm Xm Xm sperm Xm X2 female offspring Y X1 Y X2 Y male offspring Y Sex-linkage! • Sex-linked genes are found only on the X or only on the Y chromosome – Genes carried on one sex chromosome, but not on the other, are sex-linked • In humans, the X chromosome is much larger than the Y and carries over 1,000 genes • In contrast, the human Y chromosome is smaller and carries only 78 genes – During embryonic life, the action of the Y-linked gene SRY sets in motion the entire male developmental pathway • Under normal conditions, SRY causes the male gender to be linked 100 percent to the Y chromosome • Making being male a sex-linked trait Most sex linked traits are on the X – Few of the genes on the X chromosome have a specific role in female reproduction – Most of the genes on the X chromosome have no counterpart on the Y chromosome • Some genes found only on the X chromosome are important to both sexes, such as genes for color vision, blood clotting, and certain structural proteins in muscles X linked genes – allele choice difference between the sexes – The X and the Y have very few genes in common – Females (XX) can be homozygous or heterozygous for a characteristic – Males (XY) have only one copy of the genes on the X or the Y 10.7 How Are Sex and Sex-Linked Traits Inherited? • Sex-linked genes are found only on the X or only on the Y chromosome (continued) – Because females have two X chromosomes, recessive sex-linked genes on an X chromosome may or may not be expressed – Because males, with only one X chromosome, have no second copy to mask recessive genes, they fully express all the X-linked alleles they have, whether those alleles are dominant or recessive 10.7 How Are Sex and Sex-Linked Traits Inherited? • Sex-linked genes are found only on the X or only on the Y chromosome (continued) – Red-green color blindness in humans is a sex-linked trait – Color blindness is caused by recessive alleles of either of two genes located on the X chromosome – The normal, dominant alleles of these genes (called C) encode proteins that allow one set of eye cones to be most sensitive to red light and another to be most sensitive to green light 10.7 How Are Sex and Sex-Linked Traits Inherited? • Sex-linked genes are found only on the X or only on the Y chromosome (continued) – There are several defective recessive alleles of these genes, called c • The afflicted person cannot distinguish between red and green – A man can have the genotype CY or cY, which means that he has a color-vision allele C or c on his X chromosome and no corresponding gene on his Y chromosome 10.7 How Are Sex and Sex-Linked Traits Inherited? • Sex-linked genes are found only on the X or only on the Y chromosome (continued) – He will have normal color vision if his X chromosome bears the C allele, or be color-blind if his X chromosome bears the c allele – A woman may be CC, Cc, or cc because she has two X chromosomes that each can carry an allele for the trait, and will only be color-blind if her genotype is cc 10.7 How Are Sex and Sex-Linked Traits Inherited? • Sex-linked genes are found only on the X or only on the Y chromosome (continued) – A color-blind man (cY) will pass his defective allele only to his daughters because only his daughters inherit his X chromosome – A heterozygous woman (Cc), although she has normal color vision, will pass her defective allele to half her sons, who will be color-blind Figure 10-21 Sex-linked inheritance of red-green color deficiency female parent XC Xc eggs Normal color vision XC Xc The individual cannot distinguish red from green XC male parent Y Xc XC XC sperm XC XC female offspring XC Y Xc Y Y male offspring Red-green color blindness Expected children of a man with normal color vision (CY), and a heterozygous woman (Cc) Human Genetic Disorders Many human diseases are influenced by genetics • Human geneticists trying to understand the relationship between genetics and disease search medical, historical, and family records to study past crosses • Geneticists studying humans are proscribed from using breeding techniques employed with plants and other animals Records of gene expression over several generations of a family can be diagrammed (pedigree analysis) As a result, scientists now know the genes responsible for sickle-cell anemia, hemophilia, muscular dystrophy, Marfan syndrome, and cystic fibrosis Single gene traits in humans • Common traits eg. freckles, cleft chin, dimples – Each trait controlled by a single gene with a recessive and a dominant allele • Some disorders are caused by defective alleles – Defective allele may recessive or dominant Recessive allele disorders • New alleles produced by mutation usually code for nonfunctional proteins • Alleles coding for nonfunctional proteins are recessive to those coding for functional ones • The presence of one normal allele may generate enough functional protein to enable heterozygotes to be phenotypically indistinguishable from homozygotes with two normal alleles – Heterozygous individuals are carriers of a recessive genetic trait (but otherwise have a normal phenotype) – Recessive genes are more likely to occur in a homozygous combination (expressing the defective phenotype) when related individuals have children • Close relatives are more likely than the general population to each be heterozygous for a particular recessive allele and, so, are more likely to produce the homozygous recessive phenotype Eg. albinism Albinism results from a defect in melanin production • Melanin is the dark pigment that colors skin cells • Melanin is produced by the enzyme tyrosinase • An allele known as TYR (for tyrosinase) encodes a defective tyrosinase protein in skin cells, producing no melanin and a condition called albinism Albino humans and animals are homozygotes Animals homozygous for TYR have no color in their skin, fur, or eyes (the skin and hair appear white, and the eyes are pink) Figure 10-23 Albinism Human Wallaby Eg. sickle-cell anemia • caused by a defective allele for hemoglobin synthesis – – – – Hemoglobin is oxygen-transporting protein in red blood cells Mutant allele causes Hb molecules in blood cells to clump together Red blood cells have a sickle (crescent) shape and easily break Blood clots can form, leading to oxygen starvation of downstream tissues and paralysis • Considered a recessive disorder – People homozygous for the sickle-cell allele synthesize only defective hemoglobin and therefore produce mostly sickled cells Heterozygotes have about half normal and half abnormal hemoglobin, but usually have few sickled cells and usually are not seriously affected Usually only homozygotes for sickle-cell allele show symptoms – – – About 5 to 25% of sub-Saharan Africans and 8% of African Americans are heterozygous for sickle-cell anemia, but the allele is very rare in Caucasians • Most common in Africa; uncommon in Causasian populations – The large proportion of heterozygotes in Africa exists because heterozygotes have some resistance to the parasite that causes malaria – The rarity of heterozygotes in Caucasians corresponds with the rarity of malaria in northern climes, where immunity (and therefore, heterozygosity) has no selective advantage Figure 10-24 Sickle-cell anemia Normal red blood cells Sickled red blood cells Dominant allele disorders • can be transmitted to offspring if at least one parent suffers from the disease and lives long enough to reproduce – Dominant disease alleles also arise as new mutations in the DNA of eggs or sperm of unaffected parents • Various ways an allele can have dominance over the normal allele – Some dominant alleles encode an abnormal protein that interferes with the function of the normal protein – Some dominant alleles encode proteins that carry out toxic reactions – An allele may be dominant if it encodes a protein that is overactive or is active at inappropriate times and places Eg. Huntington’s Huntington disease is caused by a defective protein that kills cells in specific brain regions • Huntington disease is a dominant disorder that causes a slow, progressive deterioration of parts of the brain – The disease results in a loss of coordination, flailing movements, personality disturbances, and eventual death • The disease becomes manifest in adulthood, ensuring its maintenance in the population • The gene encodes for a protein, called “huntingtin”, of unknown function – Mutant huntingtin seems both to interfere with the action of normal huntingtin and to form large aggregates in nerve cells that ultimately kill the cells Sex linked disorders • Some human genetic disorders are sex-linked – The X chromosome contains many genes that have no counterpart on the Y chromosome – Males have only one X chromosome, so X-linked diseases tend to be more commonly seen in men Recessive sex-linked – Sex-linked disorders caused by a recessive allele have a unique pattern of inheritance • A son receives his X chromosome from his mother and passes it on only to his daughters, since the gene doesn’t exist on his Y chromosome • Sex-linked genes typically skip generations because the affected male passes the trait to a phenotypically normal carrier daughter, who in turn bears affected sons • Several defective alleles for characteristics encoded on the X chromosome are known, including red-green color blindness and hemophilia Eg. Hemophilia • Hemophilia is caused by a recessive allele on the X chromosome that results in a deficiency in one of the proteins needed for blood clotting – Hemophiliacs often have anemia owing to blood loss, and bruise easily – The hemophilia gene in Queen Victoria of England was passed among the royal families of Europe Figure 10-25 Hemophilia among the royal families of Europe Edward Duke of Kent Albert Prince of SaxeCoburg-Gotha Edward VII King of England unaffected male hemophiliac male unaffected female carrier female Victoria Princess of Saxe-Coburg Victoria Queen of England Alexandra of Denmark Leopold Duke of Albany Helen Louis IV Princess of Grand Duke of Waldeck-Pyrmont Hesse-Darmstadt Alice Princess of Hesse several unaffected children Beatrice Henry Prince of Battenburg present British royal family (unaffected) Victoria Elizabeth Alexandra Mary Tsarina carrier daughter and hemophiliac grandson Nicholas II Frederick Ernest Mary Irene of Russia Victoria ? ? ? ? Olga Tatiana Maria Anastasia Alexander Alfonso Victoria Leopold Maurice Queen Albert XII of Spain ? Alexis Tsarevitch Alfonso Crown Prince Juan Beatrice ? died Marie Jaime Gonzalo in infancy Eg. aneuploidy • Some human genetic disorders are caused by abnormal numbers of chromosomes – The incorrect separation of chromosomes or chromatids in meiosis is known as nondisjunction • Nondisjunction causes gametes to have too many and too few chromosomes – Most embryos that arise from fusion of gametes with abnormal chromosome numbers spontaneously abort, but some survive to birth and beyond Figure 10-26 Nondisjunction during meiosis Nondisjunction during meiosis I Normal meiosis Nondisjunction during meiosis II Parent cell Meiosis I Meiosis II n n n n n1 n1 n1 n1 n1 n1 n n Sex chromosome aneuploidy • Some genetic disorders are caused by abnormal numbers of sex chromosomes – Nondisjunction of sex chromosomes in males or females produces abnormal numbers of X and Y chromosomes – Nondisjunction of sex chromosomes in males produces sperm with either no sex chromosomes (called “O” sperm), or two sex chromosomes (sperm may be XX, YY, or XY) – Nondisjunction of sex chromosomes in females can produce eggs that are O or XX eggs instead of eggs with one X chromosome How do you get sex chromosome aneuploidy • Normal gametes fuse with defective sperm or eggs – the zygotes have normal numbers of autosomes but abnormal numbers of sex chromosomes • Some common abnormalities – XO, XXX, XXY, and XYY • Some sex chromosome abnormalities allow affected individuals to survive – The genes on the X chromosome are so essential to survival, any embryo without at least one X chromosome spontaneously aborts very early in development Eg. Turner’s syndrome • Turner’s syndrome (XO) occurs in females with only one X chromosome – At puberty, hormone deficiencies prevent XO females from menstruating or developing secondary sexual characteristics – Hormone treatment promotes physical development, but because affected women lack mature eggs, they remain infertile – Additional symptoms include short stature, folds of skin around the neck, and increased risk of cardiovascular disease, kidney defects, and hearing loss – Because they have only one X chromosome, women with Turner’s syndrome are more susceptible to recessive disorders such as red-green color blindness and hemophilia Eg. trisomy X (XXX) • Trisomy X (XXX) results in a fertile “normal” woman with an extra X chromosome – Most affected women show no abnormal symptoms – There is an increased chance of learning disabilities and a tendency toward tallness associated with trisomy X – By some unknown mechanism that prevents an extra X chromosome from being included in their eggs, women with trisomy X bear normal XX and XY children Eg. Klinefelter syndrome (XXY) • Men with Klinefelter syndrome (XXY) have an extra X chromosome – Most of these males show no symptoms, although some may show mixed secondary sexual characteristics, including partial breast development, broadening of the hips, and small testes – XXY men are often infertile because of low sperm count, but are not impotent – Diagnoses are made when an XXY male and his partner seek medical help because of their inability to have children Eg. Jacob syndrome (XYY) • Males with Jacob syndrome (XYY) have an extra Y chromosome (XYY) – Men with this malady have high levels of testosterone, tend to develop severe acne, and may be exceptionally tall – Jacob syndrome occurs in about 1 in every 1,000 males – Slightly increased likelihood of learning disabilities Table 10-2 Autosome aneuploidy • Some genetic disorders are caused by abnormal numbers of autosomes – Nondisjunction of autosomes can occur during meiosis in the father or mother, resulting in eggs or sperm that are missing an autosome or that have two copies of an autosome • Fusion of these gametes with a normal sperm or egg results in a zygote with one or three copies of the affected autosome • Single-copy autosome embryos usually abort very early in development How do you get this • Nondisjunction of autosomes – can occur during meiosis in the father or mother, resulting in eggs or sperm that are missing an autosome or that have two copies of an autosome • Embryos with three copies of an autosome (trisomy) also usually spontaneously abort; however, a small fraction of embryos with three copies of chromosomes 13, 18, or 21 survive to birth • The frequency of nondisjunction increases with the age of the parents Eg. trisomy 21 (Down syndrome) • In trisomy 21 (Down syndrome), afflicted individuals have three copies of chromosome 21 – Occurs in about 1 out of every 800 births – Down syndrome includes several distinctive physical characteristics, including weak muscle tone, a small mouth held partially open because it cannot accommodate the tongue, and distinctively shaped eyelids – Down syndrome is also characterized by low resistance to infectious diseases, heart malformations, and varying degrees of mental retardation, often severe Figure 10-27 Trisomy 21, or Down syndrome Karyotype showing three copies of chromosome 21 Girl with Down syndrome