Chapter 15: The Chromosomal Basis of Inheritance PDF

Chapter 15: The Chromosomal Basis of Inheritance Overview: Locating Genes Along Chromosomes - Mendel’s “hereditary factors” were genes - Today we can show that genes are located on chromosomes - The location of a particular gene can be seen by tagging isolated chromosomes with a fluoresc...

Chapter 15: The Chromosomal Basis of Inheritance Overview: Locating Genes Along Chromosomes - Mendel’s “hereditary factors” were genes - Today we can show that genes are located on chromosomes - The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene Concept 15.1: Mendelian inheritance has its physical basis in the behaviour of chromosomes - Mitosis and meiosis were first described in the late 1800s The chromosome theory of inheritance states: - Mendelian genes have specific loci (positions) on chromosomes - Chromosomes undergo segregation and independent assortment - The behaviour of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment Figure 15.2 The chromosomal basis of Mendel’s laws Morgan’s Experimental Evidence: Scientific Inquiry - The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist - Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors Morgan’s Choice of Experimental Organism Several characteristics make fruit flies a convenient organism for genetic studies - They produce many offspring - A generation can be bred every two weeks - They have only four pairs of chromosomes - Morgan noted wild type, or normal, phenotypes that were common in the fly populations - Traits alternative to the wild type are called mutant phenotypes Correlating Behaviour 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, but only males had white eyes - Morgan determined that the white-eyed mutant allele must be located on the X chromosome - Morgan’s finding supported the chromosome theory of inheritance Figure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have? - 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 - Genes on sex chromosomes exhibit unique inheritance patterns  - Linked genes: genes that are located on the same chromosome and tend to be inherited together. - Linked genes do not assort independently because they are on the same chromosome. - A dihybrid cross following two linked genes will Not produce an F2 phenotypic ratio of 9:3:3:1. Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance - In humans and some other animals, there is a chromosomal basis of sex determination The Chromosomal Basis of Sex - In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome - Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome - Females are XX, and males are XY - Each ovum contains an X chromosome, while a sperm may contain either an X or a Y chromosome - Other animals have different methods of sex determination Figure 15.6 Some chromosomal systems of sex determination. - The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features - 78 genes on Y that code for 25 proteins, ½ are expressed in the testes - A gene that is located on either sex chromosome is called a sex-linked gene - Genes on the Y chromosome are called Y-linked genes; there are few of these e.g hypertrichosis of the pinna (excessively hairy ears) - Genes on the X chromosome are called X-linked genes Figure 15.6 Some chromosomal systems of sex determination. Inheritance of X-Linked Genes - X chromosome have genes for many characters unrelated to sex, whereas the Y chromosome mainly encodes genes related to sex determination - X-linked genes follow specific patterns of inheritance For a recessive X-linked trait to be expressed - A female needs two copies of the allele (homozygous) - A male needs only one copy of the allele (hemizygous)  - X-linked recessive disorders are much more common in males than in females Figure 15.7 The transmission of X-linked recessive traits. Some disorders caused by recessive alleles on the X chromosome in humans - Color blindness (mostly X-linked) - Duchenne muscular dystrophy - Hemophilia X Inactivation in Female Mammals - In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development - The inactive X condenses into a Barr body - If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character Figure 15.8 X inactivation and the tortoiseshell cat. Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome - Each chromosome has hundreds or thousands of genes (except the Y chromosome) - Genes located on the same chromosome that tend to be inherited together are called linked genes How Linkage Affects Inheritance - Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters - Morgan crossed flies that differed in traits of body color and wing size Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters? - Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes) - He noted that these genes do not assort independently, and reasoned that they were on the same chromosome Figure 15.UN01 In-text figure, p. 294 - However, nonparental phenotypes were also produced - Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent Genetic Recombination and Linkage - The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination Recombination of Unlinked Genes: Independent Assortment of Chromosomes - Mendel observed that combinations of traits in some offspring differ from either parent - Offspring with a phenotype matching one of the parental phenotypes are called parental types - Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants - A 50% frequency of recombination is observed for any two genes on different chromosomes Figure 15.UN02 In-text figure, p. 294 Recombination of Linked Genes: Crossing Over - Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed - He proposed that some process must occasionally break the physical connection between genes on the same chromosome - That mechanism was the crossing over of homologous chromosomes Figure 15.10 Chromosomal basis for recombination of linked genes. New Combinations of Alleles: Variation for Normal Selection - Recombinant chromosomes bring alleles together in new combinations in gametes - Random fertilization increases even further the number of variant combinations that can be produced - This abundance of genetic variation is the raw material upon which natural selection works Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry - Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome - Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency - A linkage map is a genetic map of a chromosome based on recombination frequencies  - Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency - Map units indicate relative distance and order, not precise locations of genes Figure 15.11 Research Method: Constructing a Linkage Map - Genes that are far apart on the same chromosome can have a recombination frequency near 50% - Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes  - Sturtevant used recombination frequencies to make linkage maps of fruit fly genes - Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes - Cytogenetic maps indicate the positions of genes with respect to chromosomal features Figure 15.12 A partial genetic (linkage) map of a Drosophila chromosome. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders - Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders - Plants tolerate such genetic changes better than animals do Abnormal Chromosome Number - In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis - As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy Figure 15.13 Meiotic nondisjunction. - Aneuploidy results from the fertilization of gametes in which nondisjunction occurred - Offspring with this condition have an abnormal number of a particular chromosome - A monosomic zygote has only one copy of a particular chromosome - A trisomic zygote has three copies of a particular chromosome Polyploidy is a condition in which an organism has more than two complete sets of chromosomes - Triploidy (3n) is three sets of chromosomes - Tetraploidy (4n) is four sets of chromosomes - Polyploidy is common in plants, but not animals - Polyploids are more normal in appearance than aneuploids Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure - Deletion removes a chromosomal segment - Duplication repeats a segment - Inversion reverses orientation of a segment within a chromosome - Translocation moves a segment from one chromosome to another Human Disorders Due to Chromosomal Alterations - Alterations of chromosome number and structure are associated with some serious disorders - Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond - These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy Down Syndrome (Trisomy 21) - Down syndrome is an aneuploid condition that results from three copies of chromosome 21 - It affects about one out of every 700 children born in the United States - The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained flattened face and nose, a short neck, a small mouth sometimes with a large, protruding tongue, small ears, upward slanting eyes that may have small skin folds at the inner corner white spots (Brushfield spots) may be present on the colored part of the eye (iris); the hands are short and broad with short fingers, and with a single crease in the palm; poor muscle tone and loose ligaments are also common; and development and growth is usually delayed and often average height and developmental milestones are not reached. Down syndrome - Figure Aneuploidy of Sex Chromosomes - Nondisjunction of sex chromosomes produces a variety of aneuploid conditions - Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals - Taller than average, with long arms and legs  - Small testes, mostly sterile, low testosterone levels, Gynecomastia in 1/3 of patients can be reduced by mastectomy, sparse body hair, reduced muscle mass, predisposition to learning disabilities and reduction in verbal IQ (although intelligence is normal) - Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans - 45, X, female, short stature, sexual infantilism and ovarian dysgenesis, major and minor malformations - Triangle-shaped face, posteriorly rotated ears, broad webbed neck, broad shield-like chest, lymphedema of hand and feet at birth, congenital heart defects, structural kidney defects, normal intelligence - sexual infantilism : Failure to develop secondary sexual characteristics after the normal time of puberty. Disorders Caused by Structurally Altered Chromosomes - The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 - A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood - Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes Concept 15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance - There are two normal exceptions to Mendelian genetics - One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus - In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance Genomic Imprinting - For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits - Such variation in phenotype is called genomic imprinting - Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production - Forms of genomic imprinting have been demonstrated in insects, mammals and flowering plants - Genomic imprinting is an epigenetic process that involves DNA methylation and histone modifications in order to achieve monoallelic gene expression without altering the genetic sequence. These epigenetic marks are established in the germline and are maintained throughout all somatic cells of an organism. - Appropriate expression of imprinted genes is important for normal development, with numerous genetic diseases associated with imprinting defects including Angelman syndrome and Prader–Willi syndrome. - AS is a classic example of genomic imprinting in that it is caused by deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced. The sister syndrome, Prader-Willi syndrome, is caused by a similar loss of paternally inherited genes and maternal imprinting. - PWS is the most common genetic cause of obesity, owing to an involuntary urge to eat constantly coupled with a reduced need for calories. Additional non-specific symptoms are short stature, mental retardation, incomplete sexual development and behavioural problems. In infancy, PWS is characterized by severe hypotonia and feeding difficulties, both common conditions which make clinical diagnosis difficult - AS is characterised by severe mental retardation, microcephaly, seizures, characteristic abnormal behaviours (including apparent happy demeanour and hand flapping movements) and facial appearance, and severe speech limitations - It appears that imprinting is the result of the methylation (addition of –CH3) of cytosine nucleotides - Genomic imprinting is thought to affect only a small fraction of mammalian genes - Most imprinted genes are critical for embryonic development Inheritance of Organelle Genes - Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm - Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules - Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg - The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant by Karl Correns - Coloration of the offspring was determined only by the maternal parent and not by the paternal parent and is due to mutations in plastid genes - Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems - For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy