Mendelian inheritance Mendelian inheritance (or Mendelian genetics or Mendelism) is a set of primary tenets relating to the transmission of hereditary

characteristics from parent organisms to their offspring; it underlies much of genetics. They were initially derived from the work of Gregor Johann Mendel published in !"# and !"" which was $re%discovered$ in &''( and were initially very controversial. )hen they were integrated with the chromosome theory of inheritance by Thomas *unt Morgan in & #( they became the core of classical genetics.

History
Main article+ *istory of genetics The laws of inheritance were derived by Gregor Mendel(a &th century ,ustrian -riest.monk conducting hybridi/ation e0periments in garden peas (Pisum sativum).1 2 3etween !#" and !"4( he cultivated and tested some 5&(''' pea plants. 6rom these e0periments he deduced two generali/ations which later became known as Mendel's Principles of Heredity or Mendelian inheritance. *e described these principles in a two part paper( Experiments on Plant Hybridization that he read to the 7atural *istory 8ociety of 3rno on 6ebruary ! and March !( !"#( and which was published in !"".152 Mendel9s conclusions were largely ignored. ,lthough they were not completely unknown to biologists of the time( they were not seen as generally applicable( even by Mendel himself( who thought they only applied to certain categories of species or traits. , ma:or block to understanding their significance was the importance attached by &th century biologists to the apparent blending of inherited traits in the overall appearance of the progeny( now known to be due to multigene interactions( in contrast to the organ%specific binary characters studied by Mendel.1 2 ;n &''( however( his work was $re%discovered$ by three <uropean scientists( *ugo de =ries( >arl >orrens( and <rich von Tschermak. The e0act nature of the $re%discovery$ has been somewhat debated+ ?e =ries published first on the sub:ect( mentioning Mendel in a footnote( while >orrens pointed out Mendel9s priority after having read ?e =ries9s paper and reali/ing that he himself did not have priority. ?e =ries may not have acknowledged truthfully how much of his knowledge of the laws came from his own work( or came only after reading Mendel9s paper. @ater scholars have accused =on Tschermak of not truly understanding the results at all.1 2 Aegardless( the $re%discovery$ made Mendelism an important but controversial theory. ;ts most vigorous promoter in <urope was )illiam 3ateson( who coined the term $genetics$( $gene$( and $allele$ to describe many of its tenets. The model of heredity was highly contested by other biologists because it implied that heredity was discontinuous( in opposition to the apparently continuous variation observable for many traits. Many biologists also dismissed the theory because they were not sure it would apply to all species( and there seemed to be very few true Mendelian characters in nature. *owever later work by biologists and statisticians such as A.,. 6isher showed that if multiple Mendelian factors were involved in the e0pression of an individual trait( they could

produce the diverse results observed. Thomas *unt Morgan and his assistants later integrated the theoretical model of Mendel with the chromosome theory of inheritance( in which the chromosomes of cells were thought to hold the actual hereditary material( and create what is now known as classical genetics( which was e0tremely successful and cemented Mendel9s place in history. Mendel9s findings allowed other scientists to predict the e0pression of traits on the basis of mathematical probabilities. , large contribution to Mendel9s success can be traced to his decision to start his crosses only with plants he demonstrated were true%breeding. *e also only measured absolute (binary) characteristics( such as color( shape( and position of the offspring( rather than Buantitative characteristics. *e e0pressed his results numerically and sub:ected them to statistical analysis. *is method of data analysis and his large sample si/e gave credibility to his data. *e also had the foresight to follow several successive generations (f5( f4) of his pea plants and record their variations. 6inally( he performed $test crosses$ (back%crossing descendants of the initial hybridi/ation to the initial true%breeding lines) to reveal the presence and proportion of recessive characters. )ithout his hard work and careful attention to procedure and detail( Mendel9s work could not have had the impact it made on the world of genetics.

[edit] Mendel's Laws

Mendel discovered that when crossing white flower and purple flower plants( the result is not a blend. Aather than being a mi0 of the two( the offspring was purple flowered. *e then conceived the idea of heredity units( which he called $factors$( one of which is a recessive characteristic and the other dominant. Mendel said that factors( later called genes( normally occur in pairs in ordinary body cells( yet segregate during the formation of se0 cells. <ach member of the pair becomes part of the separate se0 cell. The dominant gene( such as the purple flower in Mendel9s plants( will hide the recessive gene( the white flower. ,fter Mendel self%fertili/ed the 6 generation and obtained the 4+ ratio( he correctly theori/ed that genes can be paired in three different ways for each trait+ ,,( aa( and ,a. The capital $,$ represents the dominant factor and lowercase $a$ represents the recessive. (The last combination listed above( ,a( will occur roughly twice as often as each of the other two( as it can be made in two different ways( ,a or a,.) Mendel stated that each individual has two factors for each trait( one from each parent. The two factors may or may not contain the same information. ;f the two factors are identical( the individual is called homo/ygous for the trait. ;f the two factors have different information( the individual is called hetero/ygous. The alternative forms of a factor are called alleles. The genotype of an individual is made up of the many alleles it possesses. ,n individual9s physical appearance( or phenotype( is determined by its alleles as well as by its environment. ,n individual possesses two alleles for each trait; one allele is given by the female parent and the other by the male parent. They are passed on when an individual matures and produces gametes+ egg and sperm. )hen gametes form( the paired alleles separate randomly so that each gamete receives a copy of one of the two alleles. The presence of an allele doesn9t promise that the trait will be e0pressed in the

individual that possesses it. ;n hetero/ygous individuals the only allele that is e0pressed is the dominant. The recessive allele is present but its e0pression is hidden. Mendel summari/ed his findings in two laws; the Law of Segregation and the Law of Independent Assortment.

[edit] Law of Segregation (The " irst Law"!

The @aw of 8egregation states that when any individual produces gametes( the copies of a gene separate so that each gamete receives only one copy. , gamete will receive one allele or the other. The direct proof of this was later found following the observation of meiosis by two independent scientists( the German botanist( Cscar *ertwig in !D"( and the 3elgian /oologist( <douard =an 3eneden in !!4. ;n meiosis( the paternal and maternal chromosomes get separated and the alleles with the traits of a character are segregated into two different gametes.
OR

The two coe0isting alleles of an individual for each trait segregate (separate) during gamete formation so that each gamete gets only one of the two alleles. ,lleles again unite at random fertili/ation of gametes.

[edit] Law of Independent Assortment (The "Second Law"!

The @aw of ;ndependent ,ssortment( also known as $;nheritance @aw$ states that alleles of different genes assort independently of one another during gamete formation. )hile Mendel9s e0periments with mi0ing one trait always resulted in a 4+ ratio (6ig. ) between dominant and recessive phenotypes( his e0periments with mi0ing two traits (dihybrid cross) showed &+4+4+ ratios (6ig. 5). 3ut the &+4+4+ table shows that each of the two genes are independently inherited with a 4+ phenotypic ratio. Mendel concluded that different traits are inherited independently of each other( so that there is no relation( for e0ample( between a cat9s color and tail length. This is actually only true for genes that are not linked to each other. ;ndependent assortment occurs during meiosis ; in eukaryotic organisms( specifically metaphase ; of meiosis( to produce a gamete with a mi0ture of the organism9s maternal and paternal chromosomes. ,long with chromosomal crossover( this process aids in increasing genetic diversity by producing novel genetic combinations. Cf the E" chromosomes in a normal diploid human cell( half are maternally%derived (from the mother9s egg) and half are paternally%derived (from the father9s sperm). This occurs as se0ual reproduction involves the fusion of two haploid gametes (the egg and sperm) to produce a new organism having the full complement of chromosomes. ?uring gametogenesisFthe production of new gametes by an adultFthe normal complement of E" chromosomes needs to be halved to 54 to ensure that the resulting haploid gamete can :oin with another gamete to produce a diploid organism. ,n error in the number of

chromosomes( such as those caused by a diploid gamete :oining with a haploid gamete( is termed aneuploidy. ;n independent assortment the chromosomes that end up in a newly%formed gamete are randomly sorted from all possible combinations of maternal and paternal chromosomes. 3ecause gametes end up with a random mi0 instead of a pre%defined $set$ from either parent( gametes are therefore considered assorted independently. ,s such( the gamete can end up with any combination of paternal or maternal chromosomes. ,ny of the possible combinations of gametes formed from maternal and paternal chromosomes will occur with eBual freBuency. 6or human gametes( with 54 pairs of chromosomes( the number of possibilities is 554 or !(4!!("'! possible combinations.142 The gametes will normally end up with 54 chromosomes( but the origin of any particular one will be randomly selected from paternal or maternal chromosomes. This contributes to the genetic variability of progeny.

ig"re #$ ?ominant and recessive phenotypes. ( ) -arental generation. (5) 6 generation. (4) 65 generation. ?ominant (red) and recessive (white) phenotype look alike in the 6 (first) generation and show a 4+ ratio in the 65 (second) generation

ig"re %$ The phenotypes of two independent traits show a &+4+4+ ratio in the 65 generation. ;n this e0ample( coat color is indicated by & (brown( dominant) or ' (white) while tail length is indicated by S (short( dominant) or s (long). )hen parents are homo/ygous for each trait (9SSbb and ssBB)( their children in the 6 generation are hetero/ygous at both loci and only show the dominant phenotypes. ;f the children mate with each other( in the 65 generation all combination of coat color and tail length occur+ & are brown.short (purple bo0es)( 4 are white.short (pink bo0es)( 4 are brown.long (blue bo0es) and is white.long (green bo0).

ig"re ($ The color alleles of Mirabilis jalapa are not dominant or recessive. ( ) -arental generation. (5) 6 generation. (4) 65 generation. The $red$ and $white$ allele together make a $pink$ phenotype( resulting in a +5+ ratio of red+pink+white in the 65 generation.

[edit] &ac)gro"nd
Table showing how the genes e0change according to segregation or independent assortment during meiosis and how this translates into Mendel9s laws Mendel9s law+ 6orget%me%not

The reason for these laws is found in the nature of the cell nucleus. ;t is made up of several chromosomes carrying the genetic traits. ;n a normal cell( each of these chromosomes has two parts( the chromatids. , reproductive cell( which is created in a process called meiosis( usually contains only one of those chromatids of each chromosome. 3y merging two of these cells (usually one male and one female)( the full set is restored and the genes are mi0ed. The resulting cell becomes a new embryo. The fact that this new life has half the genes of each parent (54 from mother( 54 from father for total of E" in the case of humans) is one reason for the Mendelian laws. The second most important reason is the varying dominance of different genes( causing some traits to appear unevenly instead of averaging out (whereby dominant doesn9t mean more likely to reproduceFrecessive genes can become the most common( too). There are several advantages of this method (se0ual reproduction) over reproduction without genetic e0change+ . ;nstead of nearly identical copies of an organism( a broad range of offspring develops( allowing more different abilities and evolutionary strategies. 5. There are usually some errors in every cell nucleus. >opying the genes usually adds more of them. 3y distributing them randomly over different chromosomes and mi0ing the genes( such errors will be distributed unevenly over the different children. 8ome of them will therefore have only very few such problems. This helps reduce problems with copying errors somewhat. 4. Genes can spread faster from one part of a population to another. This is for instance useful if there9s a temporary isolation of two groups. 7ew genes developing in each of the populations don9t get reduced to half when one side replaces the other( they mi0 and form a population with the advantages of both sides. E. 8ometimes( a mutation can have positive side effects. 6or e0ample( sickle cell anemia is a mutation that can causethe benefit of malaria resistance. The mechanism behind the Mendelian laws can make it possible for some offspring to carry the advantages without the disadvantages until further mutations solve the problems.

[edit] Mendelian trait

, Mendelian trait is one that is controlled by a single locus and shows a simple Mendelian inheritance pattern. ;n such cases( a mutation in a single gene can cause a disease that is inherited according to Mendel9s laws. <0amples include sickle%cell anemia( Tay%8achs disease( cystic fibrosis and 0eroderma pigmentosa. , disease controlled by a single gene contrasts with a multi%factorial disease( like arthritis( which is affected by several loci (and the environment) as well as those diseases inherited in a non%Mendelian fashion. The Mendelian ;nheritance in Man database is a catalog of( among other things( genes in which Mendelian traits cause disease.

Mendelian Genetics
*+er+iew
This module presents the basic principles of inheritance( as first outlined by Gregor Mendel. Mendel9s four postulates will be presented( and will be used to demonstrate how the genetic make%up of parents can be used to predict the characteristics of their offspring. <0amples of crosses will be presented involving one( two( and three separate genes.

*',ecti+es
. @earn the relationship between dominant and recessive alleles. 5. @earn Mendel9s four postulates( and understand how the postulates apply to the behavior of genes and chromosomes. 4. @earn how to determine the phenotypes of offspring of monohybrid( dihybrid( and trihybrid crosses. E. @earn how to use testcrosses to determine the genotypes of specific offspring from the above crosses. #. @earn to use the product law to determine the probabilities of combinations of characteristics occurring together.

-regor Mendel *umans tried for more than 5''' years to understand the principles of heredity( so that domesticated animals and plants could be bred more efficiently to e0hibit certain characteristics. The efforts to understand failed( but in spite of this( people learned to breed animals and plants empirically( with some success. 6inally( in !#"( Gregor Mendel( a monk and teacher of natural sciences( performed a successful study of inheritance in the pea plants that he tended in his garden. *ow did Mendel succeed where so many others had failedG

6irst( he made a lucky choice of an organism to study. -ea plants are easy to grow and interbreed( they grow to maturity in one year( and they can reproduce by either self%fertili/ation or by crossing between plants. 8econd( as a monk (with lots of time on his handsG)( Mendel was a meticulous record keeper. *e was able to analy/e large amounts of carefully recorded data.

Mendel published the results of his studies( but they were ignored for nearly #' years. 6inally( Mendel9s work was discovered in the early 5'th century( which led to the start of modern genetics. 8o what e0actly did Mendel doG

*e picked seven pairs of traits of pea plants( such as tall vs. dwarf plants( yellow vs. green seeds( round vs. wrinkled seeds. *e had strains of pea plants that 9bred true9 for these characteristics( meaning that (for e0ample) if a tall plant was bred with a tall plant( all of the offspring would be tall. Hsing these true breeding stocks( Mendel looked at each pair of traits separately. The Monohy'rid .ross ;n studying each pair of traits( Mendel mated two true%breeding individuals (the parental or /# generation)( each e0hibiting one of the two contrasting forms of the characteristic. 6or e0ample( if the characteristic was plant height( a dwarf plant was mated with a tall plant. The offspring of such a cross are known as the first filial or # generation. )hen 6 9s are allowed to self%fertili/e (sometimes referred to as $self$ing)( they produce an % generation.

*ere9s an e0ample of what Mendel observed+ Tall 0 1warf 6 generation+ all plants were tall 6 self%fertili/ation+ (23 of %'s were tall4 #23 were dwarf
Mendel got the same result( regardless of which parent (tall or dwarf) provided the pollen( and which parent provided the ovum. (Therefore the characteristic was independent of se0.) Mendel also observed the same result with the other characteristics+ <.g. - + round 0 wrinkled % 4.E of the 659s were round( .E wrinkled - + yellow 0 green % 4.E of the 659s were yellow( .E were green In each case that he st"died4 Mendel fo"nd a ($# ratio in the % generation5 Mendel's /ost"lates To e0plain his results( Mendel formulated three postulates+ . Genetic factors e0ist in pairs in individual organisms. ;n the above e0ample( there would be three possible pairwise combinations of the two factors. 5. )hen two unlike factors for a single characteristic are present( one factor is dominant to the other. (The other factor is considered recessive.) ;n the above e0ample( the factor for tall is dominant to the factor for dwarf.

4. ?uring gamete formation( factors segregate randomly so that each gamete receives one or the other with eBual likelihood. The offspring of an individual with one of each type of factor has an eBual chance of inheriting either factor. Mendel didn9t know the identity of his factors( because at that time cells were poorly understood. ,s we will see( Mendel9s 9factors9 are in fact genes. ,pplying Mendel9s postulates to the tall.dwarf e0ample above( Mendel reasoned that the tall and dwarf parental plants contained identical pairs of factors( because the plants bred true. ()e9ll designate 9d9 as the dwarf factor and 9?9as the tall factor.) 8o the tall plant was ?? and the dwarf plant was dd. Therefore( the 6 plants received one tall factor and one dwarf factor( making them all ?d. These plants( hetero/ygous for the one characteristic being considered( are monohy'rids. Tall is dominant to dwarf in this case( so all of the 6 9s were tall. 6 gametes would receive one factor or the other with eBual probability( so self fertili/ation would produce four possible combinations of factors in the 65+ 114 1d4 d14 dd ,ll would appear with eBual freBuency. ,ny of the plants with a ? factor would be tall; only the dd would be dwarf. Therefore( 4.E would be tall( and .E dwarf. Terminology To better discuss genetic principles( we need to introduce some new terms. @ook up each of the following terms in the glossary+

-henotype Genotype Gene ,llele )ild Type *omo/ygote *etero/ygote -roduct @aw

,nother thing to know is the /"nnett s6"are. This tool is used to predict the probability of genotypes and phenotypes occurring in the offspring of a particular mating or cross. To use a -unnett sBuare( Take the parental genotypes( and determine all of the possible combinations of alleles that could occur in gametes. @ist one parent9s gametes across the top of the sBuare( and the other parent9s gametes down the side of the sBuare. Then( within the sBuare( combine all of the possible gametes from each parent to produce all of the possible combinations of alleles in the offspring. ;9ll illustrate this by showing a -unnett sBuare of the tall.dwarf e0ample we considered+ .ross$ 1d 0 1d ( #!

;n this case( only one characteristic (plant height) is being considered. 3oth parents are hetero/ygous( and each gamete will receive one allele from the parent( ? or d. This is true of both parents in this case. )hen gametes are combined to form new individuals (in the sBuare)( we see that .E of the offspring should be ??( 5.E (or .5) should be ?d( and .E should be dd. These are the possible genotypes of the ne0t generation( and the probabilities of each occurring. This illustrates the genotypic ratio of the monohybrid cross % homo/ygous dominant + 5 hetero/ygous + homo/ygous recessive. 3ecause tall (?) is dominant to dwarf (d)( 4.E of the offspring should be tall ( and .E should be dwarf. This illustrates the phenotypic ratio of the monohybrid cross % 4 dominant + recessive. The Test .ross Cne last tool to consider+ ;f you perform the above monohybrid cross( and get the e0pected 4.E tall plants and .E dwarf plants( how can you tell which of the tall plants are homo/ygous and which are hetero/ygousG There9s no way to tell :ust by looking at the plants. To tell for sure( Mendel devised a test cross. To do a test cross( you take the individual in Buestion( and cross it to a homo7ygo"s recessi+e individual (test crosses are always done using homo/ygous recessives). To see how this works( lets consider our e0ample again. @ook at the possible results of testcrosses involving a homo/ygous dominant( and involving a hetero/ygote+ 11 1d

8o if you take a tall plant( and cross it with a homo/ygous recessive( and all of the offspring are tall plants( then you know that the tall plant in Buestion is homo/ygous. ;f(

on the other hand half of the offspring are tall and half are dwarf (a + ratio)( then the tall plant being tested is hetero/ygous. The 1ihy'rid .ross ,fter e0amining each characteristic individually( Mendel also studied them in pairs. 6or e0ample( he looked at seed shape (round vs. wrinkled) and seed color (yellow vs. green). <ach of these characteristics studied individually had shown the typical 4+ phenotypic ratio. )hen Mendel crossed true%breeding plants that produced yellow( round seeds with true breeding plants that produced green( wrinkled seeds( he observed the following results+

/#$ yellow4 ro"nd 0 green4 wrin)led

#$ all yellow4 ro"nd %$ 82#9 yellow4 ro"nd : (2#9 yellow4 wrin)led green4 wrin)led : (2#9 green4 ro"nd : #2#9

The 6 and 65 generations were identical to those shown above even if the parents were yellow( wrinkled and green( round. *ow can we e0plain the phenotypic ratio in this caseG )ell( it9s fairly straightforward if we consider it as two monohybrid crosses done separately+

Iellow (G) is dominant to green (g)( therefore the 6 9s are all yellow( and the 659s are 4.E yellow( .E green Aound ()) is dominant to wrinkled (w)( therefore the 6 9s are all round( and the 659s are 4.E round( .E wrinkled

,ccording to the -roduct @aw( the probability of getting a yellow round plant is eBual to the product of the probability of getting a yellow%seeded plant (4.E) and the probability of getting a round%seeded plant (4.E). pro'5 (yellow4 ro"nd! ; (23 0 (23 ; 82#9 The -roduct @aw can be used to e0plain the observations for the other phenotypes as well. Take a few moments and work them out.

The fact that each trait in the dihybrid cross holds to its monohybrid probabilities strongly suggests that the two characteristics do not affect each other and are therefore independent. This led Mendel to formulate a fourth postulate. Mendel's o"rth /ost"late$

?uring gamete formation( segregating pairs of genetic factors assort independently of each other.

This simply means that the factors for seed color( when they segregate during gamete formation( do not affect the segregation of the factors for seed shape( and vice versa. The entire process is random. There are two good methods for determining the theoretical outcome of any cross. Cne of these is the /"nnett s6"are. @et9s use the -unnett sBuare to ree0amine the e0ample of the dihybrid cross. ;n the dihybrid 6 plants (Gg)w)( the possible combinations of alleles in the gametes are G)( Gw( g)( and gw. 8etting this up in the -unnet sBuare+

;t is easy to see that there are si0teen allele combinations in the -unnett sBuare (although some are duplicates). >heck each genotype( determine the phenotype( and work out the phenotypic ratio. Iou should find that it matches the ratio that Mendel observed( as shown above. <ach of the fractions in the ratio is the probability that that phenotype will occur. 6or e0ample( there is a 4. " probability that any offspring will have green( round seeds. The other method for determining the outcome of a cross is the for)ed line method. This method takes advantage of the -roduct @aw( and e0ploits the fact that a cross can be broken down into a set of monohybrid crosses. The forked line method is especially useful when three or more characteristics are crossed simultaneously. 6or e0ample( a trihybrid cross would reBuire a -unnett sBuare with "E spacesJ (;f you don9t believe me( try it for yourself.) This gets to be confusing( and its easier to keep things straight using the forked line method( because it deals with phenotypes rather than genotypes.

*ere9s how the method works (using the dihybrid cross as an e0ample). ;n this case( letters will be used to designate phenotypes rather than alleles( so G means a yellow% seeded plant( g means a green%seeded plant( ) means a round%seeded plant( and w means a wrinkled%seeded plant. 6irst( we9ll consider the first characteristic( seed color. ;n a monohybrid cross (Gg 0 Gg) involving seed color( the offspring have a 4.E probability of having yellow seeds( and a .E probability of having green seeds( as shown in the diagram below. 7e0t( we9ll consider seed shape. 6or each of the color phenotypes( there9s a 4.E probability that the seeds will be round( and a .E probability that the seeds will be wrinkled. These probabilities are filled in along forked lines from the seed color probabilities. To determine the overall probability of a particular phenotype( simply multiply (i.e. use the product law) all of the probabilities along a particular line.

6or more characteristics (i.e. a trihybrid cross)( simply brach out from each point in the second column. The forked line method can also be used to determine the probabilities of particular phenotypes( but this gets more complicated( because each characteristic will have three possibilities (homo/ygous dominant( hetero/ygous( homo/ygous recessive) instead of two (dominant trait( recessive trait). 1ihy'rid Test .ross ,s with the monohybrid cross( with some of the phenotypes it seems impossible to tell what the genotype is. Iellow( round%seeded plants (GG))( Gg))( GG)w( or Gg)wG); yellow( wrinkled seeded plants (GGww or GgwwG); and green( round%seeded plants (gg)w or gg))G) are e0amples of such phenotypes. ,s with the monohybrid cross( the way to tell determine the genotype of a plant in Buestion is to do a test cross. ;n this case( the plant to be tested will be crossed with a double homo/ygous recessive( ggww. Hsing a yellow( round%seeded plant as a test sub:ect( work out all of the possible results of a test cross.

Inde> to this page

Sex

The I >hromosome o The -seudoautosomal Aegions o SR The K >hromosome K%@inkage K%;nactivation o Mechanism 8ome genes on the K chromosome escape inactivation. K%>hromosome ,bnormalities 8e0 ?etermination in Cther ,nimals <nvironmental 8e0 ?etermination *ermaphrodites

Chromosomes
The nuclei of human cells contain 55 autosomes and 5 se0 chromosomes. ;n females( the se0 chromosomes are the 5 0 chromosomes. Males have one K chromosome and one < chromosome. The presence of the I chromosome is decisive for unleashing the developmental program that leads to a baby boy.

The < .hromosome

;n making sperm by meiosis( the K and I chromosomes must separate in anaphase :ust as homologous autosomes do. This occurs without a problem because( like homologous autosomes( the K and I chromosome synapse during prophase of meiosis ;. There is a small region of homology shared by the K and I chromosome and synapsis occurs at that region. This image( courtesy of >. Tease( shows synapsis of the K and I chromosomes of a mouse during prophase of meiosis ;. >rossing over occurs in two regions of pairing( called the pse"doa"tosomal regions. These are located at opposite ends of the chromosome.

The /se"doa"tosomal =egions

The pse"doa"tosomal regions get their name because any genes located within them (so far only & have been found) are inherited :ust like any autosomal genes. Males have two copies of these genes+ one in the pseudoautosomal region of their I( the other in the corresponding portion of their K chromosome. 8o males can inherit an allele originally present on the K chromosome of their father and females can inherit an allele originally present on the I chromosome of their father. This diagram shows the structure of the human I chromosome. -enes o"tside the pse"doa"tosomal regions

,lthough &#L of the I chromosome lies between the pseudoautosomal regions( fewer than !' genes have been found here. Cver half of this region is genetically%barren heterochromatin. Cf the !'%odd genes found in the euchromatin( some encode proteins used by all cells. The others encode proteins that appear to function only in the testes. , key player in this latter group is SRY.

SRY
SR (for se0%determining region <) is a gene located on the short (p) arm :ust outside the pseudoautosomal region. ;t is the master switch that triggers the events that converts the embryo into a male. )ithout this gene( you get a female instead. )hat is the evidenceG . Cn very rare occasions aneuploid humans are born with such karyotypes as KKI( KKKI( and even KKKKI. ?espite their e0tra K chromosomes( all these cases are male. 5. This image (courtesy of Aobin @ovell% 3adge from 7ature 4# + D( && ) shows two mice with an 00 )aryotype (and thus they should be female). *owever( as you may be able to see( they have a male phenotype. This is because they are transgenic for SRY. 6ertili/ed KK eggs were in:ected with ?7, carrying the SR gene. see Making Transgenic ,nimals 4. ,lthough these mice have testes( male se0 hormones( and normal mating behavior( they are sterile. E. ,nother rarity+ KK humans with testicular tissue because a translocation has placed the SR gene on one of the K chromosomes #. 8till another rarity that demonstrates the case+ women with an KI karyotype who( despite their I chromosome( are female because of a destructive mutation in SR . (;n &&"( a test based on a molecular probe for SR was used to ensure that potential competitors for the women9s Clympic events in ,tlanta had no SR gene. 3ut because of possibilities like that in case E( this testing is no longer used to screen female Clympic athletes.)

The 0 .hromosome
The K chromosome carries hundreds of genes but few( if any( of these have anything to do directly with se0. *owever( the inheritance of these genes follows special rules. These arise because+ males have only a single K chromosome almost all the genes on the K have no counterpart on the I; thus

any gene on the K( e+en if recessi+e in females( will be e0pressed in males.

Genes inherited in this fashion are described as se0%linked or( more precisely( 0?lin)ed.

0?Lin)age$ An @>ample
Hemophilia A is a blood clotting disorder caused by a mutant gene encoding the clotting factor AIII. This gene is located on the K chromosome (shown here in red). )ith only a single K chromosome( males who inherit the defective gene (always from their mother) will be unable to produce factor =;;; and suffer from difficult%to%control episodes of bleeding. ;n hetero/ygous females( the unmutated copy of the gene will provide all the factor =;;; they need. *etero/ygous females are called "carriers" because although they show no symptoms( they pass the gene on to appro0imately half their sons( who develop the disease( and half their daughters( who also become carriers. 0 < 0 00 0< 0h 0h0 0h< )omen rarely suffer from hemophilia , because to do so they would have to inherit a defective gene from their father as well as their mother. Hntil recently( few hemophiliacs ever became fathers. >lick here for a discussion of red%green colorblindness; another e0ample of K%linked inheritance.

0?Inacti+ation
*uman females inherit two copies of every gene on the K chromosome( whereas males inherit only one (with some e0ceptions+ the & pseudoautosomal genes and the small number of $housekeeping$ genes found on the I). 3ut for the hundreds of other genes on the K( are males at a disadvantage in the amount of gene product their cells produceG The answer is no( because females have only a single acti+e K chromosome in each cell. ?uring interphase( chromosomes are too tenuous to be stained and seen by light microscopy. *owever( a dense( stainable structure( called a &arr 'ody (after its discoverer) is seen in the interphase nuclei of female mammals. The 3arr body is one of the K chromosomes. ;ts compact appearance reflects its inactivity. 8o( the cells of females have only one functioning copy of each K%linked gene F the same as males. K%inactivation occurs early in embryonic development. ;n a given cell( which of a female9s K chromosomes becomes inactivated and converted into a 3arr body is a matter

of chance (e0cept in marsupials like the kangaroo( where it is always the father9s K chromosome that is inactivated). ,fter inactivation has occurred( all the descendants of that cell will have the same chromosome inactivated. Thus K%inactivation creates clones with differing effective gene content. ,n organism whose cells vary in effective gene content and hence in the e0pression of a trait( is called a genetic mosaic.

Mechanism of 0?inacti+ation
;nactivation of an K chromosome reBuires a gene on that chromosome called XIST.

!"S# encodes a large molecule of =BA (of a type different from those( e.g.( mA7,( used in protein synthesis). !"S# A7, accumulates along the K chromosome containing the active !"S# gene and proceeds to inactivate all (or almost all) of the other hundreds of genes on that chromosome. !"S# A7, does not travel over to any other K chromosome in the nucleus. &arr 'odies are inactive K chromosomes $painted$ with !"S# A7,.

The Se6"ence of @+ents

?uring the first cell divisions of the female mouse /ygote( the !"S# locus on the father9s K chromosome is e0pressed so most of his K%linked genes are silent. 3y the time the blastocyst has formed( the silencing of the paternal K chromosome still continues in the trophoblast but in the inner cell mass (;>M) transcription of !"S# ceases on the paternal K chromosome allowing its hundreds of other genes to be e0pressed. The shut%down of the !"S# locus is done by methylating !"S# regulatory seBuences. 8o the pluripotent stem cells of the ;>M e0press both K chromosomes. *owever( as embryonic development proceeds( K%inactivation begins again. 3ut this time it is entirely random. There is no predicting whether it will be the maternal 0 or the paternal 0 that is inactivated in a given cell.

Some genes on the 0 chromosome escape inacti+ation5

)hat about those ! genes that are found on the I as well as the KG There should be no need for females to inactivate one copy of these to keep in balance with the situation in males. ,nd( as it turns out( these genes escape inactivation in females. Just how they manage this has yet to be discovered.

0?.hromosome A'normalities
,s we saw above( people are sometimes found with abnormal numbers of K chromosomes. Hnlike most cases of aneuploidy( which are lethal( the phenotypic effects of aneuploidy of the K chromosome are usually not severe. <0amples+

6emales with but a single K chromosome+ the most common cause of T"rner's syndrome. The phenotypic effects are mild because each cell has a single functioning K chromosome like those of KK females. 7umber of 3arr bodies M /ero. 000( 0000( 00000 karyotypes+ all females with mild phenotypic effects because in each cell all the e0tra K chromosomes are inactivated. 7umber of 3arr bodies M number of K chromosomes minus one. Clinefelter's syndrome+ people with KKI or KKKI karyotypes are males (because of their I chromosome). 3ut again( the phenotypic effects of the e0tra K chromosomes are mild because( :ust as in females( the e0tra Ks are inactivated and converted into 3arr bodies.

Se> 1etermination in *ther Animals

,lthough the male fruit fly( ?rosophila melanogaster( is K%I( the I chromosome does not dictate its maleness but rather the absence of a second K. 6urthermore( instead of females shutting down one K to balance the single K of the males F as we do F male flies double the output of their single K relative to that of females. ;n birds( moths( schistosomes( and some li/ards( the male has two of the same chromosome (designated NN)( whereas the female has $heterogametic$ chromosomes (designated N and )). ;n chickens( a single gene on the N chromosome (designated $MR#%)( when present in a double dose (NN)( produces males while the presence of only one copy of the gene produces females (N)).

@n+ironmental Se> 1etermination

;n some cold%blooded vertebrates some fishes many reptiles (e.g. certain snakes( li/ards( turtles( and all crocodiles and alligators) as well as in some invertebrates (e.g. certain crustaceans)( se0 is determined after fertili7ation F not by se0 chromosomes deposited in the egg. The choice is usually determined by the temperat"re at which early embryonic development takes place.

;n some cases (e.g. many turtles and li/ards)( a higher temperature during incubation favors the production of females. ;n other cases (e.g.( alligators)( a higher temperature favors the production of males.

<ven in cases (e.g. some li/ards) where there are se0 chromosomes( a high temperature can convert a genotypic male (NN) into a female.

Hermaphrodites
*ermaphrodites have both male and female se0 organs. Many species of fish are hermaphroditic. 8ome start out as one se0 and then( in response to stimuli in their environment( switch to the other. Cther species have both testes and ovaries at the same time (but seldom fertili/e themselves). (*owever( populations of >. elegans consist mostly of hermaphrodites and these only fertili/e themselves F @ink to a discussion.) *ermaphroditic fishes have no se0 chromosomes. 8<K ?<T<AM;7,T;C7 ,7? 8<K >*ACMC8CM<8 I5 A. B. C. D. E. F. G. The >hromosome Theory of ;nheritance and 8e0 @inkage Sutton and Boveri&s chromosome theory of inheritance proposed in %'()*+enes are located on chromosomes ,ust previous to this -end of %'th century. biolo/ists had discovered that half of all sperm cells carry a structure called an X body0 "n %'(1 the ! body 2ere determined to be chromosomes*X chromosomes0 #hen the chromosome 2as also discovered in %'(10 chromosomes are 3no2n as the sex chromosomes0 #o/ether the ! and

4ll other chromosomes are called autosomes0 Systems of sex chromosomes

XX!X" system #$rotenor mode

#a 5emale*!! #b Male*! #c

6ccurs in some insects li3e /rasshoppers

XX!XY System #&y'aeus mode

(a! 6emaleFKK (homogametic se0) ('! Male KI (heterogametic se0) (c! Cccurs in $rosophila( mammals and some plants

(! DD?DE System (a! 6emaleFKI (heterogametic se0) ('! MaleFKK (homogametic se0) (c! Cccurs in birds( butterflies and some fishes 3! 0?<?0< System (a! Cccurs in organisms with alteration of generations (e.g.( liverworts and

vascular plants) ('! Male gametophytesFI (c! 6emale gametophytesFK (d! 8porophytesFKI (. Morpholo/y and pairin/ of ! and
1

Each type of sex chromosome has t2o re/ions

(a! -airing region

(i! ?uring synapsis of meiotic prophase ;( the pairing regions combine (ii! 8ome genes occur in these pairing regions (iii! These genes e0hibit 0?and?< lin)age ('! ?ifferential region (i! ?ifferential regions do not pair during synapsis (ii! ?ifferential region genes are either . K%linked 5. I%linked (iii! ,ny gene K or I chromosome is said to be se> lin)ed I. Sex determination in ?rosophila
1

Sex is determined by the ratio of the number of ! chromosomes to number of autosomal sets Scheme
#a !74 8 %0(*female #b !74 8 (01*male #c

!74 9 %0(*metafemale

#d !74 : (01*metamale

).

Sex determination in humans

1 %

#he presence or absence of the

chromosome determines sex

4 /ene on the chromosome called the SRY 'ene codes for the test*s! determ*n*n' +actor
#a "t controls the production of maleness #b ;or3s by inducin/ development of the medulla of the /onadal

primordial< pairs of rid/es on the embryonic 3idneys

#c

! individuals 2ho lac3 the part of the are females

chromosomes 2ith this /ene

#d !! individuals 2ho carry a tiny piece of the

chromosome 2ith this /ene on an ! chromosome are male -thou/h sterile. thou/h perhaps the /enes there are pseudo/enes

#e #he ! chromosome contains 2hat appears to be a homolo/ous re/ion<

#+

$osa/e compensation in mammals< includin/ humans #* Bar bodies

%0 ! 44*( Barr bodies )0 !!44*% Barr body =0 !(44*( Barr bodies >0 !!!44*) Barr bodies 10 !! 44*% Barr body

#**

?yon hypothesis
. Cne K chromosome in each cell becomes inactivated early in 5. 4. E. #.

development )hich one is deactivated is random ,ll cells derived from cell with deactivated chromosome will have that chromosome deactivated This results in genetic mosaics <0amples a0 >alico cats b0 8weat gland distribution in females hetero/ygous for e0todermal dysplasia

(g! ,nomalies

(i! Hermaphrodites . *ave both ovaries and testes 5. <0ternal genitalia are ambiguous 4. Generally( true hermaphrodites are sterile( but not always E. ;n &D! (at The ,merican 8ociety of *uman Genetics meeting in =ancouver( 3.>.) as case was reported in which a0 5#%year%old hermaphrodite delivered a stillborn child after 4' weeks gestation b0 <arlier in life( this person had engaged in male se0ual activity c0 True hermaphrodites are genetic mosaicsFsome cells are KK( while others are KI (ii! /se"dohermaphrodites . -seudohermaphrodites have either testicular or ovarian tissue( but not both 5. Generally the tissue is rudimentary 4. <0ternal genitalia are often ambiguous E. 8ome are genetically female( but may look like males #. 8ome are genetically male( but may look like females and lead normal female se0 lives (iii! T"rnerFs Syndrome in h"mans (3G4 0*! . ?ue to nondis:unction in male or female parents to produce gametes without K chromosome 5. ;ncidence+ .#''' female births 4. *igh proportion of spontaneous abortions are TurnerOs and most TurnerOs individuals are aborted E. -henotypic features+ a0 8hort stature b0 )ebbed neckFweb of skin between neck and shoulders c0 3reast development absent or nearly so d0 8ome cognitive functions affected( but intelligence often about normal e0 -ubic and a0illary hair reduced or absent f0 ;nfantile genitalia /0 Hsually sterile (i+! CleinfelterFs Syndrome (3H4 00<! . ?ue to nondis:unction of K chromosome in male or female parent 5. ;ncidence+ . ''' male births

4. Tends to be maternal age effect E. 8ometimes have more than two K chromosomes #. -henotypic features

(+!
#5 %5 (5

(+i!
. 5. 4.

(+ii!
. 5. 4. E. #.

a0 @ong arms b0 3reast development c0 @ittle or no sperm production d0 8mall testes e0 Hsually mentally retarded 0<< .ondition ?ue to nondis:unction of I chromosome in male ;ncidence+ . ''' male births -henotypic features+ a0 ,bove average height b0 6ertile c0 8ometimes (but not always) retarded d0 May be correlation with delinBuency /oly?0 emales (0004 00004 000004I! ;ncidence+ . ''' female births Maternal age effect -henotypic features+ a0 8ometimes infantile genitalia b0 8ometimes underdeveloped breasts c0 6ertile d0 8ometimes mental retardation e0 ;ncidence increases with increasing number of K chromosomes Trysomy %# (3H4 00 or 0<4 J%#! ?own 8yndrome ;ncidence+ .D'' births Mild%moderate mental retardation *igh risk of leukemia -henotypic features+ a0 8hort stature b0 3rood( short skulls c0 6le0ible :oints d0 <0cess skin on the back of the neck