The following is a map of four genes on a chromosome: a) Between which two genes would you expect the lowest highest frequency of recombination?

Sex-linked Trait Problem Mendelian Genetics Sex-linked Trait Problem 4/15/2017 Example: Eye color in fruit flies (red-eyed male) x (white-eyed female) XRY x XrXr Remember: the Y chromosome in males does not carry traits. RR = red eyed Rr = red eyed rr = white eyed XY = male XX = female copyright cmassengale 3 3

Sex-linked Trait Solution: Mendelian Genetics 4/15/2017 Sex-linked Trait Solution: XR Xr Y 50% red eyed female 50% white eyed male XR Xr Xr Y copyright cmassengale 4 4

copyright cmassengale Mendelian Genetics 4/15/2017 Female Carriers copyright cmassengale 5 5

Example: Sickle cell. A mutation in a gene causes multiple symptoms Pleiotrophy Example: Sickle cell. A mutation in a gene causes multiple symptoms

Epistasis In genetics, epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes.

Polygenic Inheritance Polygenic inheritance is when a single trait is controlled by 2 or more sets of alleles. Most human traits are polygenically inherited. Examples would be skin and eye color. This explains how you can have several different phenotypes for one trait and how parents can have offspring with eye color or skin color different from what they have.

Chapter 15~ The Chromosomal Basis of Inheritance

The Chromosomal Theory of Inheritance Genes have specific loci on chromosomes and chromosomes undergo segregation and independent assortment

Chromosomal Linkage XX (female) vs. XY (male) Morgan Drosophilia melanogaster XX (female) vs. XY (male) Sex-linkage: genes located on a sex chromosome Linked genes: genes located on the same chromosome that tend to be inherited together

Classes of chromosomes autosomal chromosomes sex chromosomes

Discovery of sex linkage true-breeding red-eye female true-breeding white-eye male X P Huh! Sex matters?! 100% red eye offspring F1 generation (hybrids) 100% red-eye female 50% red-eye male 50% white eye male F2 generation

What’s up with Morgan’s flies? x x RR rr Rr Rr  r r R r R Rr Rr R RR Rr Doesn’t work that way! R Rr Rr r Rr rr 100% red eyes 3 red : 1 white

Linked genes http://bcs.whfreeman.com/thelifewire/content/chp10/1002s.swf

Genetics of Sex X Y X XX XY X XX XY In humans & other mammals, there are 2 sex chromosomes: X & Y 2 X chromosomes develop as a female: XX gene redundancy, like autosomal chromosomes an X & Y chromosome develop as a male: XY no redundancy X Y X XX XY X XX XY 50% female : 50% male

Let’s reconsider Morgan’s flies… x x XRXR XrY XRXr XRY Xr Y XR Y  XR XR XRXr XRY XRXR XRY BINGO! XR Xr XRXr XRY XRXr XrY 100% red females 50% red males; 50% white males 100% red eyes

Genetic recombination Crossing over Genes that DO NOT assort independently of each other Genetic maps The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency Linkage maps Genetic map based on recombination frequencies

Genes on sex chromosomes Y chromosome few genes other than SRY sex-determining region master regulator for maleness turns on genes for production of male hormones many effects = pleiotropy! X chromosome other genes/traits beyond sex determination mutations: hemophilia Duchenne muscular dystrophy color-blindness Duchenne muscular dystrophy affects one in 3,500 males born in the United States. Affected individuals rarely live past their early 20s. This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin. The disease is characterized by a progressive weakening of the muscles and loss of coordination.

Human sex-linkage SRY gene: gene on Y chromosome that triggers the development of testes Fathers= pass X-linked alleles to all daughters only (but not to sons) Mothers= pass X-linked alleles to both sons & daughters Sex-Linked Disorders: Color-blindness; Duchenne muscular dystropy (MD); hemophilia

Hemophilia is a sex-linked recessive trait defined by the absence of one or more clotting factors. These proteins normally slow and then stop bleeding. Individuals with hemophilia have prolonged bleeding because a firm clot forms slowly. Bleeding in muscles and joints can be painful and lead to serious damage. Individuals can be treated with intravenous injections of the missing protein.

Hemophilia XHXh XHY Hh x HH XH XHXh XH Y Xh XHXH XHXH XHY XHY XH Xh XH sex-linked recessive Hemophilia XHXh XHY Hh x HH XH XHXh XH Y male / sperm Xh XHXH XHXH XHY XHY XH Xh female / eggs XH XHY XHXh XHXh XhY XhY Y carrier disease

X-inactivation Female mammals inherit 2 X chromosomes XH XHXh Xh one X becomes inactivated during embryonic development condenses into compact object = Barr body which X becomes Barr body is random patchwork trait = “mosaic” patches of black XH XHXh Xh tricolor cats can only be female patches of orange

Human sex-linkage X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)

Chromosomal Abnormalities Errors of Meiosis Chromosomal Abnormalities 2006-2007

Chromosomal abnormalities Incorrect number of chromosomes nondisjunction chromosomes don’t separate properly during meiosis breakage of chromosomes deletion duplication inversion translocation

Nondisjunction Problems with meiotic spindle cause errors in daughter cells homologous chromosomes do not separate properly during Meiosis 1 sister chromatids fail to separate during Meiosis 2 too many or too few chromosomes 2n n-1 n n+1

Alteration of chromosome number error in Meiosis 1 error in Meiosis 2 all with incorrect number 1/2 with incorrect number

Nondisjunction Baby has wrong chromosome number~ aneuploidy trisomy cells have 3 copies of a chromosome monosomy cells have only 1 copy of a chromosome n+1 n n-1 n trisomy 2n+1 monosomy 2n-1

Human chromosome disorders High frequency in humans most embryos are spontaneously aborted alterations are too disastrous developmental problems result from biochemical imbalance imbalance in regulatory molecules? hormones? transcription factors? Certain conditions are tolerated upset the balance less = survivable but characteristic set of symptoms = syndrome

Down syndrome Trisomy 21 3 copies of chromosome 21 1 in 700 children born in U.S. Chromosome 21 is the smallest human chromosome but still severe effects Frequency of Down syndrome correlates with the age of the mother Trisomy 13 occurs in about 1 out of every 5,000 live births. It is a syndrome with multiple abnormalities, many of which are not compatible with life. More than 80% of children with trisomy 13 die in the first month. Trisomy 13 is associated with multiple abnormalities, including defects of the brain that lead to seizures, apnea, deafness, and eye abnormalities. The eyes are small with defects in the iris (coloboma ). Most infants have a cleft lip and cleft palate, and low-set ears. Congenital heart disease is present in approximately 80% of affected infants. Hernias and genital abnormalities are common. Trisomy 18 is a relatively common syndrome affecting approximately 1 out of 3,000 live births, and affecting girls more than three times as often as boys. The presence of an extra number 18 chromosome leads to multiple abnormalities. Many of these abnormalities make it hard for infants to live longer than a few months. The cri du chat syndrome is caused by the deletion of information on chromosome 5. It is likely that multiple genes on chromosome 5 are deleted. One deleted gene, called TERT (telomerase reverse transcriptase) is involved in control of cell growth, and may play a role in how some of the features of cri cu chat develop. The cause of this rare chromosomal deletion is not known, but it is expected that the majority of cases are due to spontaneous loss of a piece of chromosome 5 during development of an egg or sperm. A minority of cases result from one parent carrying a rearrangement of chromosome 5 called a translocation. Between 1 in 20,000 and 1 in 50,000 babies are affected. This disease may account for up to 1% of individuals with severe mental retardation. Infants with cri du chat syndrome commonly have a distinctive cat-like cry. They also have an extensive grouping of abnormalities, with severe mental retardation being the most important.

Sex chromosomes abnormalities Human development more tolerant of wrong numbers in sex chromosome But produces a variety of distinct syndromes in humans XXY = Klinefelter’s syndrome male XXX = Trisomy X female XYY = Jacob’s syndrome male XO = Turner syndrome female

Klinefelter’s syndrome XXY male one in every 2000 live births have male sex organs, but are sterile feminine characteristics some breast development lack of facial hair tall normal intelligence

Klinefelter’s syndrome How many Barr bodies would you expect?

Jacob’s syndrome male XYY Males 1 in 1000 live male births extra Y chromosome slightly taller than average more active normal intelligence, slight learning disabilities delayed emotional maturity normal sexual development

Trisomy X XXX 1 in every 2000 live births produces healthy females Why? Barr bodies all but one X chromosome is inactivated How many Barr bodies would you expect?

Turner syndrome Monosomy X or X0 1 in every 5000 births varied degree of effects webbed neck short stature sterile How many Barr bodies would you expect?

Changes in chromosome structure deletion loss of a chromosomal segment duplication repeat a segment inversion reverses a segment translocation move segment from one chromosome to another error of replication error of crossing over

Chromosomal errors VI Deletion Duplication Homologous chromosomes Inversion Reciprocal translocation Nonhomologous chromosomes

Genomic imprinting Def: a parental effect on gene expression Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm. Fragile X syndrome: higher prevalence of disorder and retardation in males