2The following is a map of four genes on a chromosome: a) Between which two genes would you expect the lowest highest frequency of recombination?
3Sex-linked Trait Problem Mendelian GeneticsSex-linked Trait Problem4/15/2017Example: Eye color in fruit flies(red-eyed male) x (white-eyed female) XRY x XrXrRemember: the Y chromosome in males does not carry traits.RR = red eyedRr = red eyedrr = white eyedXY = maleXX = femalecopyright cmassengale33
4Sex-linked Trait Solution: Mendelian Genetics4/15/2017Sex-linked Trait Solution:XRXrY50% red eyed female50% white eyed maleXR XrXr Ycopyright cmassengale44
6Example: Sickle cell. A mutation in a gene causes multiple symptoms PleiotrophyExample: Sickle cell. A mutation in a gene causes multiple symptoms
7EpistasisIn 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.
8Polygenic 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.
10The Chromosomal Theory of Inheritance Genes have specific loci on chromosomes and chromosomes undergo segregation and independent assortment
11Chromosomal Linkage XX (female) vs. XY (male) MorganDrosophilia melanogasterXX (female) vs. XY (male)Sex-linkage: genes located on a sex chromosomeLinked genes: genes located on the same chromosome that tend to be inherited together
12Classes of chromosomes autosomal chromosomessex chromosomes
13Discovery of sex linkage true-breedingred-eye femaletrue-breedingwhite-eye maleXPHuh! Sex matters?!100%red eye offspringF1generation(hybrids)100%red-eye female50% red-eye male50% white eye maleF2generation
14What’s up with Morgan’s flies? xxRRrrRrRrrrRrRRrRrRRRRrDoesn’t work that way!RRrRrrRrrr100% red eyes3 red : 1 white
16Genetics of Sex X Y X XX XY X XX XY In humans & other mammals, there are 2 sex chromosomes: X & Y2 X chromosomesdevelop as a female: XXgene redundancy, like autosomal chromosomesan X & Y chromosomedevelop as a male: XYno redundancyXYXXXXYXXXXY50% female : 50% male
17Let’s reconsider Morgan’s flies… xxXRXRXrYXRXrXRYXrYXRYXRXRXRXrXRYXRXRXRYBINGO!XRXrXRXrXRYXRXrXrY100% red females50% red males; 50% white males100% red eyes
18Genetic recombination Crossing over Genes that DO NOT assort independently of each otherGenetic maps The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequencyLinkage maps Genetic map based on recombination frequencies
19Genes on sex chromosomes Y chromosomefew genes other than SRYsex-determining regionmaster regulator for malenessturns on genes for production of male hormonesmany effects = pleiotropy!X chromosomeother genes/traits beyond sex determinationmutations:hemophiliaDuchenne muscular dystrophycolor-blindnessDuchenne 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.
20Human sex-linkageSRY gene: gene on Y chromosome that triggers the development of testesFathers= pass X-linked alleles to all daughters only (but not to sons)Mothers= pass X-linked alleles to both sons & daughtersSex-Linked Disorders: Color-blindness; Duchenne muscular dystropy (MD); hemophilia
21Hemophilia 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.
22Hemophilia XHXh XHY Hh x HH XH XHXh XH Y Xh XHXH XHXH XHY XHY XH Xh XH sex-linked recessiveHemophiliaXHXhXHYHh x HHXHXHXhXHYmale / spermXhXHXHXHXHXHYXHYXHXhfemale / eggsXHXHYXHXhXHXhXhYXhYYcarrierdisease
23X-inactivation Female mammals inherit 2 X chromosomes XH XHXh Xh one X becomes inactivated during embryonic developmentcondenses into compact object = Barr bodywhich X becomes Barr body is randompatchwork trait = “mosaic”patches of blackXHXHXhXhtricolor cats can only be femalepatches of orange
24Human sex-linkageX-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)
25Chromosomal Abnormalities Errors of MeiosisChromosomal Abnormalities
26Chromosomal abnormalities Incorrect number of chromosomesnondisjunctionchromosomes don’t separate properly during meiosisbreakage of chromosomesdeletionduplicationinversiontranslocation
27NondisjunctionProblems with meiotic spindle cause errors in daughter cellshomologous chromosomes do not separate properly during Meiosis 1sister chromatids fail to separate during Meiosis 2too many or too few chromosomes2nn-1nn+1
28Alteration of chromosome number error in Meiosis 1error in Meiosis 2all with incorrect number1/2 with incorrect number
29Nondisjunction Baby has wrong chromosome number~ aneuploidy trisomy cells have 3 copies of a chromosomemonosomycells have only 1 copy of a chromosomen+1nn-1ntrisomy2n+1monosomy2n-1
30Human chromosome disorders High frequency in humansmost embryos are spontaneously abortedalterations are too disastrousdevelopmental problems result from biochemical imbalanceimbalance in regulatory molecules?hormones?transcription factors?Certain conditions are toleratedupset the balance less = survivablebut characteristic set of symptoms = syndrome
31Down syndromeTrisomy 213 copies of chromosome 211 in 700 children born in U.S.Chromosome 21 is the smallest human chromosomebut still severe effectsFrequency of Down syndrome correlates with the age of the motherTrisomy 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.
32Sex chromosomes abnormalities Human development more tolerant of wrong numbers in sex chromosomeBut produces a variety of distinct syndromes in humansXXY = Klinefelter’s syndrome maleXXX = Trisomy X femaleXYY = Jacob’s syndrome maleXO = Turner syndrome female
33Klinefelter’s syndrome XXY maleone in every 2000 live birthshave male sex organs, but are sterilefeminine characteristicssome breast developmentlack of facial hairtallnormal intelligence
34Klinefelter’s syndrome How many Barr bodies would you expect?
35Jacob’s syndrome male XYY Males 1 in 1000 live male births extra Y chromosomeslightly taller than averagemore activenormal intelligence, slight learning disabilitiesdelayed emotional maturitynormal sexual development
36Trisomy X XXX 1 in every 2000 live births produces healthy females Why?Barr bodiesall but one X chromosome is inactivatedHow many Barr bodies would you expect?
37Turner syndrome Monosomy X or X0 1 in every 5000 births varied degree of effectswebbed neckshort staturesterileHow many Barr bodies would you expect?
38Changes in chromosome structure deletionloss of a chromosomal segmentduplicationrepeat a segmentinversionreverses a segmenttranslocationmove segment from one chromosome to anothererror of replicationerror of crossing over
39Chromosomal errors VI Deletion Duplication Homologous chromosomes InversionReciprocal translocationNonhomologous chromosomes
40Genomic 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