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 behavior 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 behavior of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment

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 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, 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

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

            The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features

            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

            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

            Genes on the X chromosome are called X-linked genes

Inheritance of X-Linked Genes

            X chromosomes 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

            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

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

            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

            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

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

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

            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

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

            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

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

            Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans

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

            It appears that imprinting is the result of the methylation (addition of —CH3) of cysteine 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