NOTES: Ch 15 - , Sex Determination & Overview: Locating on Chromosomes

● A century ago the relationship between genes and chromosomes was not obvious ● Today we can show that genes are located on chromosomes ● The location of a particular can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene The Theory of Inheritance states that:

● Mendelian genes have specific loci (positions) on chromosomes ● It is the chromosomes that undergo segregation and independent assortment! P Generation Yellow-round Green-wrinkled seeds (YYRR) seeds (yyrr)

Meiosis

Fertilization

Gametes

All F1 plants produce yellow-round seeds (YyRr)

F1 Generation

Meiosis LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT Two equally probable arrangements of chromosomes at metaphase I

Anaphase I

Metaphase II

Gametes

F2 Generation Fertilization among the F1 plants Morgan’s Experimental Evidence: Scientific Inquiry

● The first solid evidence associating a specific gene with a a specific chromosome came from , an embryologist Morgan’s Choice of Experimental Organism: Fruit Flies!

● Characteristics that make fruit flies a convenient organism for genetic studies: -They breed at a high rate -A generation can be bred every two weeks -They have only four pairs of chromosomes

● Morgan noted WILD TYPE, or normal, that were common in the fly populations ● Traits alternative to the wild type are called mutant phenotypes

Correlating Behavior of a Gene’s with Behavior of a Chromosome Pair

● In one experiment, Morgan mated male flies with 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-eye mutant must be located on the ● Morgan’s finding supported the chromosome theory of inheritance! P Generation

F1 Generation

F2 Generation

P Generation

Ova (eggs) Sperm

F1 Generation

Ova (eggs) Sperm

F2 Generation

The Big Question…

● It may be easy to see that genes located on DIFFERENT chromosomes assort independently but what about genes located on the SAME chromosome? Thomas Morgan’s Research

● Morgan identified more than 50 genes on Drosophila’s 4 chromosomes. ● He discovered that many seemed to be “linked” together – They are almost always inherited together & only rarely become separated ● Grouped genes into 4 linkage groups

Morgan’s Conclusion:

● Each chromosome is actually a group of linked genes ● BUT Mendel’s principle of independent assortment still holds true ● It is the chromosomes that assort independently!! – Mendel missed this because 6 of the 7 traits he studied were on different chromosomes. So…

● If 2 genes are found on the same chromosome are they linked forever? – NO!! ● CROSSING OVER during Meiosis can separate linked genes Testcross Gray body, Black body, parents normal wings vestigial wings

(F1 dihybrid) (double mutant)

Replication of Replication of chromosomes chromosomes

Meiosis I: Crossing over between b and vg loci produces new allele combinations.

Meiosis I and II: No new allele combinations are produced.

Meiosis II: Separation of chromatids produces recombinant gametes Recombinant with the new allele chromosomes combinations. Ova Sperm

Gametes

Ova

Testcross 965 944 206 185 offspring Wild type Black- Gray- Black- Sperm (gray-normal) vestigial vestigial normal Recombination 391 recombinants =  100 = 17% frequency 2,300 total offspring

Parental-type offspring Recombinant offspring Gene Maps ● Alfred Sturtevant was a graduate student working in Morgan’s lab part-time in 1911 ● He hypothesized that the farther apart 2 genes are on a chromosome the more likely they are to be separated by Alfred crossing-over Sturtevant ● The rate of at which linked 1891-1970 genes are separated can be used to produce a “map” of distances between genes

Gene Maps

● This map shows the relative locations of each known gene on a chromosome Linkage Maps

● 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 Recombination frequencies

9% 9.5%

17%

b cn vg Chromosome I

IV II Y X III

Mutant phenotypes

Short Black Cinnabar Vestigial Brown aristae body eyes wings eyes

0 48.5 57.5 67.0 104.5

Long aristae Gray Red Normal Red (appendages body eyes wings eyes on head)

Wild-type phenotypes Sex-linked genes exhibit unique patterns of inheritance

● In humans and other animals, there is a chromosomal basis of sex determination ● Human somatic cells contain 23 pairs of chromosomes -22 pairs of (same in males & females) -1 pair of sex chromosomes (XX or XY) -Females have 2 matching sex chromosomes: XX -Males are XY Inheritance of Sex-Linked Genes ● The sex chromosomes have genes for many characters unrelated to sex ● A gene located on either is called a SEX-LINKED gene ● Sex-linked genes follow specific patterns of inheritance Sperm Sperm Sperm

Ova Ova Ova ● Some disorders caused by recessive alleles on the X chromosome in humans: - -Duchenne -Hemophilia

● When a gene is located on the X chromosome, females receive 2 copies of the gene, and males receive only 1 copy – Example: Color-blindness (c) is recessive to normal vision (C), and it is located on the X chromosome; hemophilia

EXAMPLE PROBLEM: ● A female heterozygous for normal vision: (we say she has normal vision, but is a carrier of the colorblindness allele) XC Xc

● A male who is colorblind: Xc Y What is the probability that: a) they will have a son who is colorblind? b) they will have a daughter who is colorblind? c) their first son will be colorblind? d) their first daughter will be carrier? XC Xc a) 1/4 (25%) b) 1/4 (25%) c XC Xc Xc Xc X c) 1/2 (50%) d) 1/2 (50%) Y XC Y Xc Y EXAMPLE PROBLEM:

● Hemophilia is a hereditary disease in which the blood clotting process if defective. Classic hemophilia results from an abnormal or missing clotting factor VIII; it is inherited as an X-linked recessive disorder (h).

● If a man without hemophilia and a woman who is a carrier of the hemophilia allele have children, what is the probability that…

XH Y x XH Xh what is the probability that: a) they will have a daughter with hemophilia?

b) they will have a son with hemophilia?

c) their first son will have hemophilia?

d) their first daughter will be a carrier? XH Xh a) 0/4 (0%) b) 1/4 (25%) H XH XH XH Xh X c) 1/2 (50%) d) 1/2 (50%) Y XH Y Xh Y Pedigree Charts Queen Victoria’s Legacy in Royal Families of Europe

X-inactivation in Female Mammals

● In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development ● If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character Two cell populations in adult cat:

Active X

Early embryo: Orange X chromosomes fur Cell division Inactive X and X chromosome Inactive X inactivation Allele for Black orange fur fur Allele for Active X black fur Tortoise-shell cats! (a.k.a. “Torties”) XBXb So, what about the ?

Alterations of chromosome number or structure cause some genetic disorders

● Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders 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 Meiosis I

Nondisjunction

Meiosis II

Nondisjunction

Gametes

n + 1 n + 1 n – 1 n – 1 n + 1 n – 1 n n Number of chromosomes

Nondisjunction of homologous Nondisjunction of sister chromosomes in meiosis I chromatids in meiosis I ● Aneuploidy results from the fertilization of gametes in which nondisjunction occurred ● Offspring with this condition have an abnormal number of a particular chromosome ● a TRISOMIC zygote has three copies of a particular chromosome ● a MONOSOMIC zygote has only one copy of a particular chromosome ● Polyploidy is a condition in which an organism has more than two complete sets of chromosomes 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 a segment within a chromosome -Translocation moves a segment from one chromosome to another Deletion A deletion removes a chromosomal segment.

Duplication A duplication repeats a segment.

An inversion reverses a segment Inversion within a chromosome.

A translocation moves a segment from one chromosome to another, Reciprocal nonhomologous one. translocation 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:

● 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

Aneuploidy of Sex Chromosomes

● Nondisjunction of sex chromosomes produces a variety of aneuploid conditions ● 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:

● One 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 Normal chromosome 9 Reciprocal Translocated chromosome 9 translocation

Philadelphia chromosome

Normal chromosome 22 Translocated chromosome 22