Chapter 15

The Chromosomal Basis of Inheritance

Lecture Outline
Overview: Locating Genes Along Chromosomes
Today we know that genesGregor Mendels hereditary factorsare located on chromosomes. A century ago, the relationship etween genes and chromosomes was not so o !ious. Many iologists were skeptical a out Mendels laws of segregation and independent assortment until e!idence mounted that they had a physical asis in the eha!ior of chromosomes.

Concept 15.1 Men elian inheritance has its ph!sical "asis in the "ehavior of chromosomes.
Around "#$$, cytologists and geneticists egan to see parallels etween the eha!ior of chromosomes and the eha!ior of Mendels factors. o %sing impro!ed microscopy techni&ues, cytologists worked out the process of mitosis in "'() and meiosis in the "'#$s. o *hromosomes and genes are oth present in pairs in diploid cells. o +omologous chromosomes separate and alleles segregate during meiosis. o ,ertili-ation restores the paired condition for oth chromosomes and genes. Around "#$., /alter 0utton, Theodor 1o!eri, and others noted these parallels, and a chromosome theor! of inheritance egan to take form2 o Genes occupy specific loci on chromosomes. o *hromosomes undergo segregation during meiosis. o *hromosomes undergo independent assortment during meiosis. The eha!ior of homologous chromosomes during meiosis can account for the segregation of the alleles at each genetic locus to different gametes. The eha!ior of nonhomologous chromosomes can account for the independent assortment of alleles for two or more genes located on different chromosomes. 3n the early .$th century, Thomas +unt Morgan was the first geneticist to associate a specific gene with a specific chromosome. 4ike Mendel, Morgan made an insightful choice in his e5perimental animal. Morgan worked with Drosophila melanogaster, a fruit fly that eats fungi on fruit. o ,ruit flies are prolific reeders and ha!e a generation time of two weeks. o ,ruit flies ha!e three pairs of autosomes and a pair of se5 chromosomes 677 in females, 78 in males9.
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Morgan spent a year looking for !ariant indi!iduals among the flies he was reeding. +e disco!ered a single male fly with white eyes instead of the usual red. The normal character phenotype is called the wil t!pe. ,or a gi!en character in flies, the genes sym ol is chosen from the first mutant disco!ered. The allele for white eyes in Drosophila is sym oli-ed y w. A superscript identifies the wild@type 6red@eye9 allele 6w+9. The sym ols for human genes are capital letters 6for e5ample, HD for the allele for +untingtons disease9.

Alternati!e traits are called mutant phenotypes ecause they are due to alleles that originate as mutations in the wild@type allele. /hen Morgan crossed his white@eyed male with a red@eyed female, all the , " offspring had red eyes, suggesting that the red allele was dominant to the white allele. *rosses etween the ," offspring produced the classic B2" phenotypic ratio in the ,. offspring. o 0urprisingly, the white@eyed trait appeared in only , . males. All the ,. females and half the ,. males had red eyes. Morgan concluded that a flys eye color was linked to its se5.

Morgan deduced that the gene with the white@eyed mutation is on the 7 chromosome, with no corresponding allele present on the 8 chromosome. o ,emales 6779 may ha!e two red@eyed alleles and ha!e red eyes or may e hetero-ygous and ha!e red eyes. o Males 6789 ha!e only a single allele. They will ha!e red eyes if they ha!e a red@eyed allele or white eyes if they ha!e a white@eyed allele. Morgans finding of the correlation etween a particular trait and an indi!iduals se5 pro!ided support for the chromosome theory of inheritance. o A specific gene 6for eye color9 is carried on a specific chromosome 6the 7 chromosome9.

Concept 15.# $e%&lin'e genes e%hi"it (ni)(e patterns of inheritance.

Although the anatomical and physiological differences etween women and men are numerous, the chromosomal asis of se5 is rather simple. o o 3n humans and other mammals, there are two !arieties of se5 chromosomes, 7 and 8. An indi!idual who inherits two 7 chromosomes usually de!elops as a female. An indi!idual who inherits an 7 and a 8 chromosome usually de!elops as a male.

0hort segments at either end of the 8 chromosome are the only regions that are homologous with the corresponding regions of the 7. o These homologous regions allow the 7 and 8 chromosomes in males to pair and eha!e like homologous chromosomes during meiosis in the testes. 3n oth testes 6789 and o!aries 6779, the two se5 chromosomes segregate during meiosis, and each gamete recei!es one. o =ach o!um recei!es an 7 chromosome. o +alf the sperm cells recei!e an 7 chromosome, and half recei!e a 8 chromosome.
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Therefore, each conception has a out a fifty@fifty chance of producing a particular se5. 3f a sperm cell earing an 7 chromosome fertili-es an o!um, the resulting -ygote is female 6779. 3f a sperm cell earing a 8 chromosome fertili-es an o!um, the resulting -ygote is male 6789. :ther animals ha!e different methods of se5 determination. The 7@$ system is found in some insects. ,emales are 77 and males are 7. 3n irds, some fishes, and some insects, females are C/ and males are CC. 3n ees and ants, females are diploid and males are haploid.

3n humans, the anatomical signs of se5 first appear when the em ryo is a out two months old. A 1efore that, the gonads can de!elop into either testes or o!aries. 3n "##$, a 1ritish research team identified a gene on the 8 chromosome re&uired for the de!elopment of testes. o They named the gene SRY 6se5@determining region of the 8 chromosome9. o 3n indi!iduals with the SRY gene, the generic em ryonic gonads de!elop into testes. The SRY gene codes for a protein that regulates many other genes, triggering a cascade of iochemical, physiological, and anatomical features. 3n indi!iduals lacking the SRY gene, the generic em ryonic gonads de!elop into o!aries.

3n the 7@8 system, the 8 chromosome is much smaller than the 7 chromosome. <esearchers ha!e se&uenced the 8 chromosome and identified (' genes coding for a out .) proteins. o +alf of the genes are e5pressed only in the testes, and some are re&uired for normal testicular function. o 0ome genes on the 8 chromosome are necessary for the production of functional sperm. o 3n the a sence of these genes, an 78 indi!idual is male ut does not produce normal sperm. 3n addition to their role in determining se5, the se5 chromosomes, especially the 7 chromosome, ha!e genes for many characters unrelated to se5. A gene located on either se5 chromosome is called a se%&lin'e gene. 3n humans, the term sex-linked gene refers to a gene on the 7 chromosome.

+uman se5@linked genes follow the same pattern of inheritance as Morgans white@eye locus in Drosophila. o ,athers pass se5@linked alleles to all their daughters ut none of their sons. o Mothers pass se5@linked alleles to oth sons and daughters. 3f a se5@linked trait is due to a recessi!e allele, a female will e5press this phenotype only if she is homo-ygous. o +etero-ygous females are carriers for the recessi!e trait. 1ecause males ha!e only one 7 chromosome (hemizygous ! any male who recei!es the recessi!e allele from his mother will e5press the recessi!e trait. The chance of a female inheriting a dou le dose of the mutant allele is much less than the chance of a male inheriting a single dose. o Therefore, males are far more likely to e5hi it se5@linked recessi!e disorders than are
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females. o o o o o ,or e5ample, color lindness is a mild disorder inherited as a se5@linked trait. A color@ lind daughter may e orn to a color@ lind father whose mate is a carrier. The odds of this happening are fairly low. 0e!eral serious human disorders are se5@linked. *(chenne m(sc(lar !stroph! affects one in B,)$$ males orn in the %nited 0tates. Affected indi!iduals rarely li!e past their early .$s. This disorder is due to the a sence of an 7@linked gene for a key muscle protein called dystrophin. The disease is characteri-ed y a progressi!e weakening of the muscles and a loss of coordination.

+emophilia is a se5@linked recessi!e disorder defined y the a sence of one or more proteins re&uired for lood clotting. o These proteins normally slow and then stop leeding. o 3ndi!iduals with hemophilia ha!e prolonged leeding ecause a firm clot forms slowly. o 1leeding in muscles and Doints can e painful and can lead to serious damage. A Today, people with hemophilia can e treated with intra!enous inDections of the missing protein.

Although female mammals inherit two 7 chromosomes, only one 7 chromosome is acti!e. Therefore, males and females ha!e the same effecti!e dose 6one copy9 of genes on the 7 chromosome. Euring female de!elopment, one 7 chromosome per cell condenses into a compact o Dect called a Barr "o !. o Most of the genes on the 1arr@ ody chromosome are not e5pressed. A The condensed 1arr@ ody chromosome is reacti!ated in o!arian cells that produce o!a. Mary 4yon, a 1ritish geneticist, demonstrated that selection of which 7 chromosome will form the 1arr ody occurs randomly and independently in em ryonic cells at the time of 7 inacti!ation. As a conse&uence, females consist of a mosai" of two types of cells, some with an acti!e paternal 7 chromosome and others with an acti!e maternal 7 chromosome. o After an 7 chromosome is inacti!ated in a particular cell, all mitotic descendants of that cell will ha!e the same inacti!e 7. o 3f a female is hetero-ygous for a se5@linked trait, appro5imately half her cells will e5press one allele, and the other half will e5press the other allele. 3n humans, this mosaic pattern is e!ident in women who are hetero-ygous for an 7@ linked mutation that pre!ents the de!elopment of sweat glands. o A hetero-ygous woman has patches of normal skin and patches of skin that lacks sweat glands. 0imilarly, the orange@and@ lack pattern on tortoiseshell cats is due to patches of cells e5pressing an orange allele while other patches ha!e a non@orange allele. 7 inacti!ation in!ol!es modification of the EFA y the attachment of methyl 6*+ B9 groups to one of the nitrogenous ases on the 7 chromosome that will ecome the 1arr ody.
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<esearchers ha!e disco!ered a gene called #$S% 67@inacti!e specific transcript9. This gene is acti!e only on the 1arr@ ody chromosome and produces multiple copies of an <FA molecule that attach to the 7 chromosome on which they were made. This initiates 7 inacti!ation. The mechanism that connects #$S% <FA and EFA methylation is unknown. /hat determines which of the two 7 chromosomes has an acti!e #$S% gene is also unknown.

Concept 15., Lin'e genes ten to "e inherite together "eca(se the! are locate near each other on the same chromosome.
=ach chromosome has hundreds or thousands of genes. Genes located on the same chromosome that tend to e inherited together are called lin'e genes. The results of crosses with linked genes differ from those e5pected according to the law of independent assortment. Morgan o ser!ed this linkage and its de!iations when he followed the inheritance of characters for ody color and wing si-e in Drosophila. o The wild@type ody color is gray 6&+9, and the mutant is lack 6&9. o The wild@type wing si-e is normal 6'g+9, and the mutant has !estigial wings 6'g9. The mutant alleles are recessi!e to the wild@type alleles. Feither gene is on a se5 chromosome.

Morgan crossed ," hetero-ygous females 6&+&'g+'g9 with homo-ygous recessi!e males 6&&'g'g9. According to independent assortment, this should produce four phenotypes in a "2"2"2" ratio. 0urprisingly, Morgan o ser!ed a large num er of wild@type 6gray@normal9 and dou le@ mutant 6 lack@!estigial9 flies among the offspring. o These phenotypes are those of the parents. Morgan reasoned that ody color and wing shape are usually inherited together ecause the genes for these characters are on the same chromosome. The other two phenotypes 6gray@!estigial and lack@normal9 were rarer than e5pected ased on independent assortment 6 ut totally une5pected from dependent assortment9.

/hat led to this genetic recom"ination- the production of offspring with new com inations of traitsG Independent assortment of chromosomes produces genetic recombination of unlinked genes. Genetic recom ination can result from independent assortment of genes located on nonhomologous chromosomes. Mendels dihy rid cross e5periments produced offspring that had a com ination of traits that did not match either parent in the ? generation. o 3f the ? generation consists of a yellow@round seed parent 6 YYRR9 crossed with a green@ wrinkled seed parent 6yyrr9, all the ," plants ha!e yellow@round seeds 6YyRr9. o A cross etween an ," plant and a homo-ygous recessi!e plant 6a testcross9 produces four
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phenotypes. +alf are the parental t!pes- with phenotypes that match the original ? parents, with either yellow@round seeds or green@wrinkled seeds. +alf are recom"inant t!pes or recom"inants- new com inations of parental traits, with yellow@wrinkled or green@round seeds.

A )$H fre&uency of recom ination is o ser!ed for any two genes located on different 6nonhomologous9 chromosomes. The physical asis of recom ination etween unlinked genes is the random orientation of homologous chromosomes at metaphase 3 of meiosis, which leads to the independent assortment of alleles. The ," parent 6YyRr9 produces gametes with four different com inations of alleles2 YR, Yr, yR, and yr. o The orientation of the tetrad containing the seed@color gene has no earing on the orientation of the tetrad with the seed@shape gene. Crossing over produces genetic recombination of linked genes. 3n contrast, linked genes, genes located on the same chromosome, tend to mo!e together through meiosis and fertili-ation. %nder normal Mendelian genetic rules, we would not e5pect linked genes to recom ine into assortments of alleles not found in the parents. The results of Morgans testcross for ody color and wing shape did not conform to either independent assortment or complete linkage. o %nder independent assortment, the testcross should produce a "2"2"2" phenotypic ratio. o %nder complete linkage, we should e5pect to see a "2"2$2$ ratio, with only parental phenotypes among the offspring. Most of the offspring had parental phenotypes, suggesting linkage etween the genes. +owe!er, a small percentage of the flies were recom inants, suggesting incomplete linkage. Morgan proposed that some mechanism must occasionally reak the physical connection etween genes on the same chromosome. This process, called crossing over- accounts for the recom ination of linked genes.

*rossing o!er occurs while replicated homologous chromosomes are paired during prophase of meiosis 3. o :ne maternal and one paternal chromatid reak at corresponding points and then reDoin with each other. The occasional production of recom inant gametes during meiosis accounts for the occurrence of recom inant phenotypes in Morgans testcross. The percentage of recom inant offspring, the re"om&ination (re)uen"y! is related to the distance etween linked genes. Geneticists can use recombination data to map a chromosomes genetic loci. :ne of Morgans students, Alfred 0turte!ant, used the crossing o!er of linked genes to de!elop a method for constructing a genetic map- an ordered list of the genetic loci along a particular chromosome. 0turte!ant hypothesi-ed that the fre&uency of recom inant offspring reflects the distance
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etween genes on a chromosome. +e assumed that crossing o!er is a random e!ent and that the chance of crossing o!er is appro5imately e&ual at all points on a chromosome. 0turte!ant predicted that the (arther apart two genes are! the higher the pro&a&ility that a "rosso'er will o""ur &etween them and! there(ore! the higher the re"om&ination (re)uen"y. o The greater the distance etween two genes, the more points there are etween them where crossing o!er can occur. 0turte!ant used recom ination fre&uencies from fruit fly crosses to map the relati!e positions of genes along chromosomes. A genetic map ased on recom ination fre&uencies is called a lin'age map. 0turte!ant used the testcross design to map the relati!e positions of three fruit fly genes2 ody color 6&9, wing si-e 6'g9, and eye color 6"n9. o *inna ar 6"n9, one of many Drosophila genes affecting eye color, results in a right red eye. o The recom ination fre&uency etween "n and & is #H. o The recom ination fre&uency etween "n and 'g is #.)H. o The recom ination fre&uency etween & and 'g is "(H. o The only possi le arrangement of these three genes places the eye@color gene etween the other two. 0turte!ant e5pressed the distance etween genes, the recom ination fre&uency, as map (nits. o :ne map unit 6called a "entimorgan9 is e&ui!alent to a "H recom ination fre&uency. 8ou may notice that the three recom ination fre&uencies in our mapping e5ample are not &uite additi!e2 #H 6&@"n9 I #.)H 6"n@'g9 J "(H 6&@'g9. This results from multiple crossing@ o!er e!ents. o A second crossing o!er cancels out the first and reduces the o ser!ed num er of recom inant offspring. o Genes father apart 6for e5ample, &@'g9 are more likely to e5perience multiple crossing@ o!er e!ents. 0ome genes on a chromosome are so far apart that a crosso!er etween them is !irtually certain. 3n this case, the fre&uency of recom ination reaches its ma5imum !alue of )$H and the genes eha!e as if found on separate chromosomes. o 3n fact, two genes studied y Mendelfor seed color and flower colorare located on the same chromosome ut still assort independently. o 0uch genes are physi"ally linked, ecause they are on the same chromosome, ut geneti"ally unlinked, ecause they sort independently on each other. Genes located far apart on a chromosome are mapped y adding the recom ination fre&uencies etween the distant genes and the inter!ening genes. 0turte!ant and his colleagues were a le to map the linear positions of genes in Drosophila into four groups, one for each chromosome. o o A linkage map pro!ides an imperfect picture of a chromosome. Map units indicate relati!e distance and order, not precise locations of genes. The fre&uency of crossing o!er is not actually uniform o!er the length of a chromosome.
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 1y com ining linkage maps with other methods like chromosomal anding, geneticists can de!elop c!togenetic maps of chromosomes. o These maps indicate the positions of genes with respect to chromosomal features. <ecent techni&ues show the physical distances etween gene loci in EFA nucleotides.

Concept 15.. Alterations of chromosome n(m"er or str(ct(re ca(se some genetic isor ers.
?hysical and chemical distur ances can damage chromosomes in maDor ways. =rrors during meiosis can alter the num er of chromosomes in a cell. ?lants tolerate genetic defects to a greater e5tent than do animals. /on is0(nction occurs when pro lems with the meiotic spindle cause errors in daughter cells. o FondisDunction may occur if tetrad chromosomes do not separate properly during meiosis 3. o Alternati!ely, sister chromatids may fail to separate during meiosis 33. As a conse&uence of nondisDunction, one gamete recei!es two of the same type of chromosome, and another gamete recei!es no copy. :ffspring resulting from the fertili-ation of a normal gamete with one produced y nondisDunction ha!e an a normal chromosome num er, a condition known as ane(ploi !. o Trisomic cells ha!e three copies of a particular chromosome type and ha!e . n I " total chromosomes. o Monosomic cells ha!e only one copy of a particular chromosome type and ha!e . n " chromosomes. 3f the organism sur!i!es, aneuploidy typically leads to a distinct phenotype. Aneuploidy can also occur during failures of the mitotic spindle.

3f this happens early in de!elopment, the aneuploid condition is passed along y mitosis to a large num er of cells. o This is likely to ha!e a su stantial effect on the organism. :rganisms with more than two complete sets of chromosomes are pol!ploi . ?olyploidy may occur when a normal gamete fertili-es another gamete in which there has een nondisDunction of all its chromosomes. o The resulting -ygote is triploid 6Bn9. Alternati!ely, if a .n -ygote fails to di!ide after replicating its chromosomes, a tetraploid 6Kn9 em ryo results from su se&uent successful cycles of mitosis. ?olyploidy is relati!ely common among plants and much less common among animals, although it is known to occur in fishes and amphi ians. o The spontaneous origin of polyploid indi!iduals plays an important role in the e!olution of plants. o Many crop plants are polyploid. ,or e5ample, ananas are triploid and wheat is he5aploid 6Ln9. o <ecently, researchers in *hile identified a new rodent species that may e tetraploid.
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?olyploids are more nearly normal in phenotype than aneuploids.

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:ne e5tra or missing chromosome apparently upsets the genetic alance during de!elopment more than does an entire e5tra set of chromosomes. 1reakage of a chromosome can lead to four types of changes in chromosome structure. A eletion occurs when a chromosome fragment lacking a centromere is lost during cell di!ision. This chromosome will e missing certain genes. A (plication occurs when a fragment ecomes attached as an e5tra segment to a sister chromatid. Alternati!ely, a detached fragment may attach to a nonsister chromatid of a homologous chromosome. 3n this case, the duplicated segments will not e identical if the homologs carry different alleles. An inversion occurs when a chromosomal fragment reattaches to the original chromosome, ut in the re!erse orientation. 3n translocation- a chromosomal fragment Doins a nonhomologous chromosome. Eeletions and duplications are especially likely to occur during meiosis. +omologous chromatids may reak and reDoin at incorrect places during crossing o!er, so that one chromatid loses more genes than it recei!es. The products of such a nonre"ipro"al crosso!er are one chromosome with a deletion and one chromosome with a duplication.

o o o o

A diploid em ryo that is homo-ygous for a large deletion or a male with a large deletion to its single 7 chromosome is usually missing many essential genes. o This is usually lethal. Euplications and translocations are typically harmful. <eciprocal translocation or in!ersion can alter phenotype ecause a genes e5pression is influenced y its location among neigh oring genes. Human disorders are due to chromosome alterations. 0e!eral serious human disorders are due to alterations of chromosome num er and structure. Although the fre&uency of aneuploid -ygotes may e &uite high in humans, most of these alterations are so disastrous to de!elopment that the em ryos are spontaneously a orted long efore irth. o 0e!ere de!elopmental pro lems result from an im alance among gene products. *ertain aneuploid conditions upset the alance less, making sur!i!al to irth and eyond possi le. o 0ur!i!ing indi!iduals ha!e a set of symptomsa syndromecharacteristic of the type of aneuploidy. o Genetic disorders caused y aneuploidy can e diagnosed efore irth y fetal testing. :ne aneuploid condition, *own s!n rome- is due to three copies of chromosome .", or trisomy *+. o Trisomy ." affects one in ($$ children orn in the %nited 0tates. Although chromosome ." is the smallest human chromosome, trisomy ." se!erely alters an indi!iduals phenotype in specific ways. o 3ndi!iduals with Eown syndrome ha!e characteristic facial features, short stature, heart
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defects, suscepti ility to respiratory infection, mental retardation, and increased risk of de!eloping leukemia and Al-heimers disease. Most are se5ually underde!eloped and sterile.

Most cases of Eown syndrome result from nondisDunction during gamete production in one parent. o The fre&uency of Eown syndrome increases with the age of the mother. Trisomy ." may e linked to some age@dependent a normality in a meiosis 3 checkpoint that normally delays anaphase until all the kinetochores are attached to the spindle.

Trisomies of other chromosomes also increase in incidence with maternal age, ut it is rare for infants with these autosomal trisomies to sur!i!e for long. FondisDunction of se5 chromosomes produces a !ariety of aneuploid conditions in humans. o o o o This aneuploidy upsets the genetic alance less se!erely that autosomal aneuploidy. This may e ecause the 8 chromosome contains relati!ely few genes and ecause e5tra copies of the 7 chromosome ecome inacti!ated as 1arr odies in somatic cells. An 778 male has ,line(elter-s syndrome, which occurs once in e!ery .,$$$ li!e irths. These indi!iduals ha!e male se5 organs ut a normally small testes and are sterile. Although the e5tra 7 is inacti!ated, some reast enlargement and other female characteristics are common. Affected indi!iduals ha!e normal intelligence. Males with an e5tra 8 chromosome 67889 tend to e somewhat taller than a!erage.

Trisomy 7 67779, which occurs once in e!ery .,$$$ li!e irths, produces healthy females. o o o o o o Monosomy 7, or %urner syndrome 67$9, occurs once in e!ery ),$$$ irths. This is the only known !ia le monosomy in humans. 7$ indi!iduals are phenotypically female ut are sterile ecause their se5 organs do not mature. /hen gi!en estrogen replacement therapy, girls with Turner syndrome de!elop secondary se5 characteristics. Most ha!e normal intelligence. 0tructural alterations of chromosomes can also cause human disorders. Eeletions, e!en in a hetero-ygous state, can cause se!ere pro lems. :ne syndrome, "ri du "hat, results from a specific deletion in chromosome ). These indi!iduals are mentally retarded, ha!e small heads with unusual facial features, and ha!e a cry like the mewing of a distressed cat. This syndrome is fatal in infancy or early childhood.

*hromosomal translocations etween nonhomologous chromosomes are also associated with human disorders. *hromosomal translocations ha!e een implicated in certain cancers, including "hroni" myelogenous leukemia (./0 . o *M4 occurs when a large fragment of chromosome .. switches places with a small fragment from the tip of chromosome #. o The resulting short, easily recogni-ed chromosome .. is called the 1hiladelphia
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"hromosome.

Concept 15.5 $ome inheritance patterns are e%ceptions to the stan ar chromosome theor!.
The phenotypic effects of some mammalian genes depend on hether they are inherited from the mother or the father. ,or most genes, it is a reasona le assumption that a specific allele will ha!e the same effect whether it is inherited from the mother or the father. ,or a few do-en mammalian traits, phenotype !aries depending on which parent passed along the alleles for those traits. o The genes in!ol!ed are not necessarily se5@linked and may or may not lie on the 7 chromosome. Mariation in phenotype depending on whether an allele is inherited from the male or female parent is called genomic imprinting. Genomic imprinting occurs during the formation of gametes and results in the silencing of certain genes. o 3mprinted genes are not e5pressed. 1ecause different genes are imprinted in sperm and o!a, some genes in a -ygote are maternally imprinted and others are paternally imprinted. o These maternal and paternal imprints are transmitted to all ody cells during de!elopment. o ,or a maternally imprinted gene, only the paternal allele is e5pressed. o ,or a paternally imprinted gene, only the maternal allele is e5pressed. ?atterns of imprinting are characteristic of a gi!en species. The gene for insulin@like growth factor . 6$g(*9 was one of the first imprinted genes to e identified. Although the growth factor is re&uired for normal prenatal growth, only the paternal allele is e5pressed. =!idence that the $g(* allele is imprinted initially came from crosses etween wild@type mice and dwarf mice homo-ygous for a recessi!e mutation in the $g(* gene. o The phenotypes of hetero-ygous offspring differ, depending on whether the mutant allele comes from the mother or the father. o The $g(* allele is imprinted in eggs, turning off e5pression of the imprinted allele. o 3n sperm, the $g(* allele is not imprinted and functions normally. 3n many cases, the genomic imprint consists of methyl 6*+ B9 groups that are added to the cytosine nucleotides of one of the alleles. The hypothesis that methylation directly silences an allele is consistent with the e!idence that hea!ily methylated genes are usually inacti!e. o :ther mechanisms may lead to silencing of imprinted genes. o ,or a few genes, howe!er, methylation has een shown to a"ti'ate e5pression of the allele. o This is the case for the $g(* gene2 Methylation of certain EFA nucleotides on the paternal chromosome leads to e5pression of the paternal $g(* allele.
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Most of the known imprinted genes are critical for em ryonic de!elopment.

3n e5periments with mice, em ryos engineered to inherit oth copies of certain chromosomes from the same parent die efore irth, whether their lone parent is male or female. 3n .$$K, scientists in Napan com ined the genetic material from two eggs in a -ygote, while allowing e5pression of the $g(* gene from only one of the egg nuclei. Formal de!elopment re&uires that em ryonic cells ha!e one acti!e copy of certain genes. A errant imprinting is associated with a normal de!elopment and certain cancers.

!"tranuclear genes e"hibit a non#$endelian pattern of inheritance. Fot all of a eukaryote cells genes are located on nuclear chromosomes, or e!en in the nucleus. 2xtranu"lear or "ytoplasmi" genes are found in small circles of EFA in mitochondria and chloroplasts. These organelles reproduce themsel!es and transmit their genes to daughter organelles. Their cytoplasmic genes do not display Mendelian inheritance ecause they are not distri uted to offspring according to the same rules that direct the distri ution of nuclear chromosomes during meiosis. Oarl *orrens first o ser!ed cytoplasmic genes in plants in "#$#, when he studied the inheritance of patches of yellow or white on the lea!es of an otherwise green plant. *orrens determined that this !ariegation was due to mutations in plastid genes that control pigmentation. o 3n most plants, a -ygote recei!es all of its plastids from the egg cytoplasm. o As a result, the maternal parent determines the coloration of the offsprings lea!es. 1ecause a -ygote inherits all its mitochondria from the o!um, all mitochondrial genes in most animals and plants demonstrate maternal inheritance. o o o o o o o o 0e!eral rare human disorders are produced y mutations to mitochondrial EFA. These disorders affect primarily the AT? supply y producing defects in the electron transport chain or AT? synthase. Tissues that re&uire large energy supplies 6the ner!ous system and muscles9 may suffer energy depri!ation from these defects. ,or e5ample, a person with mito"hondrial myopathy suffers weakness, intolerance of e5ercise, and muscle deterioration. Another mitochondrial disorder is 0e&er-s hereditary opti" neuropathy! which can produce sudden lindness in young adults. The four mutations that ha!e een found thus far to cause this disorder affect o5idati!e phosphorylation during cellular respiration, clearly a crucial function for the cell. :ther mitochondrial mutations may contri ute to dia etes, heart disease, and other diseases of aging, such as Al-heimers disease. :!er a lifetime, new mutations gradually accumulate in mitochondrial EFA. 0ome researchers think that these mutations play a role in the normal aging process.

4ecture :utline for *amp ell;<eece Biology, 'th =dition, > ?earson =ducation, 3nc.

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