* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The Chromosomal Basis of Inheritance
Long non-coding RNA wikipedia , lookup
Biology and sexual orientation wikipedia , lookup
Gene desert wikipedia , lookup
Essential gene wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Saethre–Chotzen syndrome wikipedia , lookup
History of genetic engineering wikipedia , lookup
Segmental Duplication on the Human Y Chromosome wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Genome evolution wikipedia , lookup
Minimal genome wikipedia , lookup
Ridge (biology) wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Gene expression profiling wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Gene expression programming wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Genomic imprinting wikipedia , lookup
Genome (book) wikipedia , lookup
Y chromosome wikipedia , lookup
The Chromosomal Basis of Inheritance Chapter 15 Genes and Chromosomes Genes Are located on chromosomes Can be visualized using certain techniques Figure 15.1 Introduction In 1875 process of Mitosis and in 1890 Meiosis was worked out But not until 1900 did biology finally catch up with Gregor Mendel Independently, Karl Correns, Erich von Tschermak, and Hugo de Vries all found that Mendel had explained the same results 35 years before But there was still resistance Around 1900, cytologists and geneticists began to see parallels between the behavior of chromosomes and the behavior of Mendel’s factors Chromosomes and genes are both present in pairs in diploid cells Homologous chromosomes separate and alleles segregate during meiosis Fertilization restores the paired condition for both chromosomes and genes. Chromosomal Theory of Inheritance In 1902, Walter Sutton, Theodor Boveri, and others noted these parallels and a chromosome theory of inheritance began to take form Chromosomal Theory of Inheritance Researchers proposed in the early 1900s that genes are located on chromosomes The chromosome theory of inheritance states that Mendelian genes have specific loci on chromosomes Chromosomes undergo segregation and independent assortment Behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment Evidence that Genes Associated to Chromsomes Thomas Hunt Morgan was the first to associate a specific gene with a specific chromosome He provided convincing evidence that chromosomes are the location of Mendel’s heritable factors Experimental animal, Drosophila melanogaster, a fruit fly species that eats fungi on fruit. Fruit flies prolific breeders generation time of two weeks. Fruit flies three pairs of autosomes and a pair of sex chromosomes (XX in females, XY in males). Wild Type and Mutant Phenotypes After a year of research Morgan discovered a mutant /variant (traits alternative to the wild type)male fly with White eyes Wild type Red eyes Figure 15.3 Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair In one experiment Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) The F1 generation all had red eyes The F2 generation showed the 3:1 red:white eye ratio The white-eyed trait appeared only in males. All the females and half the males had red eyes Morgan concluded that a fly’s eye color was linked to its sex Morgan concluded that a fly’s eye color was linked to its sex Females (XX) may have two red-eyed alleles and have red eyes or may be heterozygous and have red eyes. Males (XY) have only a single allele and will be red eyed if they have a red-eyed allele or whiteeyed if they have a whiteeyed allele. Morgan’s Discovery That transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color trait Was the first solid evidence indicating that a specific gene is associated with a specific chromosome Figure 15.3 Linkage of Genes Affects Inheritance Each chromosome Has hundreds or thousands of genes Genes located on the same chromosome, linked genes, tend to be inherited together because the chromosome is passed along as a unit Morgan did other experiments with fruit flies To see how linkage affects the inheritance of two different characters Inheritance of Characters for Body Color and Wing Size The wild-type body color is gray (b+) and the mutant black (b) The wild-type wing size is normal (vg+) and the mutant has vestigial wings (vg) P Generation b+b+vg+vg+ (gray, normal wing) X bbvgvg (black, vestigeal wings) Crossed F1 heterozygous females (b+bvg+vg) with homozygous recessive males (bbvgvg). Fig. 15.4 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Results According to independent assortment, this should produce 4 phenotypes in a 1:1:1:1 ratio Observed a large number of wild-type (gray-normal) and double-mutant (blackvestigial) flies among the offspring These phenotypes correspond to those of the parents Morgan Reasoned That body color and wing shape are usually inherited together because their genes are on the same chromosome The other two phenotypes (grayvestigial and blacknormal) were fewer than expected from independent assortment (and totally unexpected from dependent assortment). These new phenotypic variations must be the result of crossing over Genetic Recombination and Linkage Recombination of Unlinked Genes: Independent Assortment of Chromosomes When Mendel followed the inheritance of two characters He observed two parental phenotypes and two non parental phenotypes (Recombinants) Gametes from yellow-round heterozygous parent (YyRr) YR Gametes from greenwrinkled homozygous recessive parent (yyrr) yr Yr yR Yyrr yyRr yr YyRr yyrr Parentaltype offspring Recombinant offspring Recombinant offspring Are those that show new combinations of the parental traits When 50% of all offspring are recombinants Geneticists say that there is a 50% frequency of recombination Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked But due to the appearance of recombinant phenotypes, the linkage appeared incomplete Morgan proposed that Some process must occasionally break the physical connection between genes on the same chromosome Crossing over of homologous chromosomes was the mechanism Linkage Mapping Morgan’s student Alfred Sturtevant, used crossing over of linked genes to develop a method for constructing a chromosome map. This map is an ordered list of the genetic loci along a particular chromosome Sturtevant hypothesized frequency of recombinant offspring reflected the distances between genes on a chromosome The farther apart two genes are, the higher the probability that a crossover will occur between them and therefore a higher recombination frequency. The greater the distance between two genes, the more points between them where crossing over can occur. He used recombination frequencies from fruit fly crosses to map the relative position of genes along chromosomes, a linkage map (the actual map of a chromosome based on recombination frequencies) Map of Fruit Fly Genes The test cross design to map the relative position of three fruit fly genes, body color (b), wing size (vg), and eye color (cn). The recombination frequency between cn and b is 9%. The recombination frequency between cn and vg is 9.5%. The recombination frequency between b and vg is 17%. The only possible arrangement of these three genes places the eye color gene between the other two. Map Units Sturtevant expressed the distance between genes, the recombination frequency, as map units. One map unit (sometimes called a centimorgan) is equivalent to a 1% recombination frequency Genetic Map of a Drosophila Chromosome Cytological Maps A linkage map provides an imperfect picture of a chromosome Map units relative distance and order, not precise locations of genes. The frequency of crossing over is not actually uniform over the length of a chromosome. Geneticists can develop cytological maps indicates the positions of genes with respect to chromosomal features. More recent techniques show the absolute distances between gene loci in DNA nucleotides. The Chromosomal Basis of Sex The Chromosomal basis for determining sex is rather simple The X-Y System The X-O System The Z-W System The haploid-diploid System The X-Y System Female homogameticXX Male heterogametic XY Sex of offspring depends on whether the sperm has an X The X-Y System The Y and X chromosomes behave as homologous chromosomes during meiosis. In reality, they are only partially homologous and rarely undergo crossing over. In both testes (XY) and ovaries (XX), the two sex chromosomes segregate during meiosis and each gamete receives one. Each egg receives an X chromosome. Half the sperm receive an X chromosome and half receive a Y chromosome. Because of this, each conception has about a fifty-fifty chance of producing a particular sex. The X-Y System In humans, the anatomical signs of sex the embryo is about two months old, before that the gonads can develop into either ovaries or testes, depending on the hormonal conditions within the embryo Also,which of these two occurs depends on the Y chromosome Researchers have found the SRY gene (sex determining region of the Y chromosome In individuals with the SRY gene the generic embryonic gonads are modified into testes, Activity of the SRY gene triggers a cascade of biochemical, physiological, and anatomical features because it regulates many other genes. In addition, other genes on the Y chromosome are necessary for the production of functional sperm. In individuals lacking the SRY gene, the generic embryonic gonads develop into ovaries. The X-O System In insects Only one type of chromosome Females XX, Males XO Sex of off spring sperm has X or O The Z-W System In birds, some fishes and some insects Females ZW, Males ZZ Sex chromosome is in the ovum The haploid-diploid System No sex chromosomes inmost species of ants and bees Females fertilized ova diploid Males unfertilized ova haploid Inheritance of Sex Linked Genes The sex chromosomes have genes for many characters unrelated to sex A gene located on either sex chromosome a sex-linked • A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation. If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder. If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele. Human Sex linked Disorders Some recessive alleles found on the X chromosome in humans cause certain types of disorders Color blindness Duchenne muscular dystrophy Hemophilia Color blindness Sex linked disorder due to several X-linked genes(recessive) Normal Vision 150 colors Colorblind fewer than 25 colors Affected People RED & GREEN Gray RED & GREEN Weak confuse shades Color Blindness Normal Female XX Color Blind XcXc Normal,Carrier XcX Normal Male X Y c Color Blind Male X Y Normal Father & Color Blind Mother All daughters are carriers, sons are color blind X Y Xc X Xc X Xc Xc X Xc Xc Y Normal Mother & Color Blind Father All daughters are carriers, sons are normal Xc Y X X Xc XY X X Xc XY Duchenne’s Muscular Dystrophy Affects 1/ 3,500 males born in the US Affected individuals rarely live past their early 20s Due to absence of X-linked gene that makes a protein dystrophin Disease progressive weakening of muscles & loss of coordination Hemophilia Sex linked recessive trait Absence of one or more clotting factors in the blood Gene that controls formation of clotting factors are recessive and present on the X chromosome Individuals bleed excessively when injured Approx. 1/10,000 males are affected Hemophilia Female Hemophiliacmust have this trait on both the XX Male only one X chromosome from mother, will be a hemophiliac if mother has this trait Ex: Queen Victoria’s genes Queen Victoria & Hemophilia Victoria Albert Alexandra Alexandra & Hemophilia Czar Nicholas II Alexandra Alexis X Inactivation Although female mammals inherit two X chromosomes, only one X chromosome is active. Therefore, males and females have the same effective dose (one copy ) of genes on the X chromosome. During female development, one X chromosome per cell condenses into a compact object, a Barr body. This inactivates most of its genes. The condensed Barr body chromosome is reactivated in ovarian cells that produce ova. Barr Bodies Mary Lyon, a British geneticist the selection of which X chromosome to form the Barr body occurs randomly and independently in embryonic cells at the time of X inactivation Females consist of a mosaic of cells, some with an active paternal X, others with an active maternal X. After Barr body formation, all descendent cells have the same inactive X. If a female is heterozygous for a sex-linked trait, approximately half her cells will express one allele and the other half will express the other allele. In humans, this mosaic pattern is evident in women who are heterozygous for a X-linked mutation that prevents the development of sweat glands. A heterozygous woman will have patches of normal skin and skin patches lacking sweat glands. Barr Bodies Similarly, the orange and black pattern on tortoiseshell cats is due to patches of cells expressing an orange allele while others have a nonorange allele. X Inactivation X inactivation involves the attachment of methyl (CH3) groups to cytosine nucleotides on the X chromosome that will become the Barr body. One of the two X chromosomes has an active XIST gene (X-inactive specific transcript). This gene produces multiple copies of an RNA molecule that almost cover the X chromosome where they are made. This initiates X inactivation, but the mechanism that connects XIST RNA and DNA methylation is unknown. What determines which of the two X chromosomes will have an active XIST gene is also unknown. Alteration of Chromosome Number and Genetic Disorders Sex-linked traits are not the only notable deviation from the inheritance patterns observed by Mendel Also, gene mutations are not the only kind of changes to the genome that can affect phenotype Physical and chemical disturbances, errors in meiosis damage chromosomes and alter #s Large-scale chromosomal alterations lead to spontaneous abortions or cause a variety of developmental disorders Abnormal Chromosome Numbers Members of the pair of homologous chromosomes do not move apart Aneuploidy offspring have an abnormal number of a particular chromosome Trisomy three copies of a particular chromosome Monosomy only one copy of a particular Polyploidy Is a condition in which there are chromosome more than two complete sets of chromosomes (3n,4n) Nondisjunction Occurs when problems with the meiotic spindle cause errors in daughter cells. If tetrad chromosomes do not separate properly during meiosis I. Or sister chromatids may fail to separate during meiosis II Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure Deletion Duplication Inversion Translocation Deletion A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division. This chromosome will be missing certain genes. Duplication A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid Inversion Occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation. Translocation a chromosomal fragment joins a nonhomologous chromosome. Some translocations are reciprocal, others are not. Human Disorders Due to Chromosomal Alterations Several serious human disorders are due to alterations of chromosome number and structure. Although the frequency of aneuploid zygotes may be quite high in humans, most of these alterations are so disastrous that the embryos are spontaneously aborted long before birth. These developmental problems results from an imbalance among gene products. Certain aneuploid conditions upset the balance less, leading to survival to birth and beyond. These individuals have a set of symptoms - a syndrome characteristic of the type of aneuploidy. Trisomy 21 Abnormal Chromosome number If not drastic individuals carrying it can be born Results from an error during meiosis Affects 1/700 children born in the US Downs Syndrome Extra chromosome on # 21 This affects phenotype Facial features Broad round face Flattened nose Small irregular teeth Stature usually short Heart defects Susceptible to infection, leukemia, Alzheimer’s Life span shorter Varying degrees of mental retardation Aneuploidy of Sex Chromosomes Klinefelter’s syndrome, an XXY male, occurs once in every 2000 live births. These individuals have male sex organs, but are sterile. There may be feminine characteristics, but their intelligence is normal Males with an extra Y chromosome (XYY) tend to somewhat taller than average Aneuploidy of Sex Chromosomes Trisomy X (XXX), occurs once in every 2000 live births, produces healthy females. Monosomy X or Turner’s syndrome (X0), occurs once in every 5000 births, produces phenotypic, but immature females. Disorders due to Structurally Altered Chromosomes Deletions, even in a heterozygous state, cause severe physical and mental problems. One syndrome, cri du chat, results from a specific deletion in chromosome 5. These individuals are mentally retarded, have a small head with unusual facial features, and a cry like the mewing of a distressed cat. This syndrome is fatal in infancy or early childhood Structurally Altered Chromosomes Chromosomal translocations between nonhomologous chromosome are also associated with human disorders. Chromosomal translocations have been implicated in certain cancers, including chronic myelogenous leukemia (CML). CML occurs when a fragment of chromosome 22 switches places with a small fragment from the tip of chromosome 9 Normal chromosome 9 Reciprocal translocation Translocated chromosome 9 Philadelphia chromosome Normal chromosome 22 Translocated chromosome 22 Inheritance Patterns that are exceptions to the standard chromosome theory Two normal exceptions to Mendelian genetics include Genes located in the nucleus Genes located outside the nucleus Genomic Imprinting In this process, a gene on one homologous chromosome is silenced, while its allele on the homologous chromosome is expressed. The imprinting status of a given gene depends on whether the gene resides in a female or a male. The same alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm. Genomic imprinting Involves the silencing of certain genes that are “stamped” with an imprint during gamete production Normal Igf2 allele (expressed) Paternal chromosome Maternal chromosome Normal Igf2 allele Wild-type mouse with imprint (normal size) (not expressed) (a) A wild-type mouse is homozygous for the normal igf2 allele. Normal Igf2 allele Paternal Maternal Mutant lgf2 allele Normal size mouse Mutant lgf2 allele Paternal Maternal Figure 15.17a, b Dwarf mouse Normal Igf2 allele with imprint (b) When a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size. But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype. Inheritance of Organelle Genes Extranuclear genes Are genes found in organelles in the cytoplasm The inheritance of traits controlled by genes present in the chloroplasts or mitochondria Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg Figure 15.18 Some diseases affecting the muscular and nervous systems Are caused by defects in mitochondrial genes that prevent cells from making enough ATP Genomic Imprinting