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com
MUTATION
(4 hour)
Retold by:
Amran Md Said,
Matriculation College of Pahang.
Obecti!e. At the end of thi" to#ic, "tudent" "hould be able to:
$%#lain mutation
Cla""ify mutation
"tate ty#e" of mutation
define mutagen
"tate ty#e" of mutagen
e%#lain gene&#oint mutation
cla""ify gene mutation
de"cribe ba"e "ub"titution a" #oint mutation eng. Sic'le cell anemia
e%#lain frame"hift mutation
de"cribe ba"e in"ertion a" a frame"hift mutation
de"cribe ba"e deletion a" a frame"hif mutation
e%#lain chromo"omal mutation
cla""ify chromo"omal mutation
e%#lain chromo"omal aberration ("tructural change")
"tate and de"cribe ty#e of chromo"omal aberration
e%#lain alteration of chromo"ome number
"tate the ty#e" of the alteration
e%#lain aneu#loidy
de"cribe the cau"e and the affect aneu#loidy
e%#lain auto"omal abnormalitie" and their effect"
e%#lain "e% chromo"omal abnormalitie"
e%#lain eu#loidy
e%#lain #oly#loidy
What is mutation?
A mutation i" a change in the amount, arrangement or "tructure of the ()A of an organi"m.
Mutation" #roduce "udden and di"tinct difference" bet*een indi!idual" cau"e alternation of
chromo"ome.
Alteration of chromo"ome number or "tructure cau"e "ome genetic di"order" "uch a" Sic'le Cell
Anemia and (o*n Syndrome
Mutation can occurring in gamete cell" or "omatic cell".
i) gamete cell"
are inherited, +t #a""ed to "ub"e,uent generation" a" #art of the hereditary endo*ment of the
game" deri!ed from that cell.
ii) "omatic cell"
can only be inherited by daughter cell" #roduced by mito"i".
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A mutant i" an indi!idual or ne* genetic character ari"ing or re"ulting from an in"tance of mutation the
blue lob"ter i" an e%am#le of a mutant.

-y#e of mutation
i) "#ontaneou" mutation
. Mi"ta'e" ha##en "#ontaneou"ly during ()A re#lication, re#air and recombination
. eg. nondi"unction
ii) induced mutation
. Organi"m e%#o"ed to mutagen
What is mutagen ?
a mutagen (/atin, literally origin of change) i" a #hy"ical or chemical agent that change" the genetic
material
O#erate either by cau"ing change" in the ()A of the gene" or by cau"ing chromo"ome damage
ty#e of mutagen
i) Phy"ical agent
0ltra!iolet ray
+oni1ing radiation (2.ray, gamma ray, al#ha #article", neutron and electron)
ii) Chemical agent
eg. Colchicine (u"ually to treat rheumatic com#laint", e"#ecially gout)
$thidium bromide (i" an intercalating agent commonly u"ed a" a fluore"cent tag in laboratorie" for
techni,ue" "uch a" agaro"e gel electro#hore"i")
CLASSIFICATION OF MUTATION:
Cla""ify of mutation
i) gene & #oint mutation
ii) chromo"omal mutation
GENE MUTATION (POINT MUTATION) GENE MUTATION (POINT MUTATION)
Producing alteration" in the "e,uence of ()A nucleotide.
in!ol!e only one or a fe* ba"e #air in the coding "e,uence.
Ari"e due to "#ontaneou" #airing error" that occur during ()A re#lication,
Ari"e due to mutagen" li'e radiation or chemical" cau"e damage to the ()A.
A" a re"ult :
. Change the amino acid "e,uence and thu", change" the #rotein
. (ifferent #rotein #roduced a" the effect of mutation may not function a" normal
Cla""ify gene mutation
i) 3a"e "ub"titution
ii) 3a"e in"ertion
iii) 3a"e deletion
i!) 3a"e in!er"ion
mutation of ba"e deletion and in"ertion ma'e cau"e frame "hift mutation
Alteration of gene mutation cau"e "ome genetic di"order" "uch a" Sic'le Cell Anemia
Cassi!i"ation o! Gene Cassi!i"ation o! Gene mutation: mutation:
#ase su$stitution :
One or a fe* ba"e #air" in the nucleotide "e,uence" in gene" i" "ub"titute
Change" in ba"e "e,uence 4 re"ult" in change" of codon (0A0&050)
6 ba"e& nucleic acid 7 8 codon (coding for 8 amino acid)
Change" in codon:.
a) amino acid change" (mi""en"e mutation)
b) change" a codon to "to# codon (non"en"e mutation)
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Mi""en"e mutation" are tho"e that "till code for an amino acid but change the indicated amino acid eg.
Sic'le Cell Anemia.
)on"en"e mutation" c )on"en"e mutation" change an amino acid codon into a "to# codon, nearly al*ay" leading to a
nonfunctional #rotein.
Si"%e "e Anemia Si"%e "e Anemia
mutant 9b
"
cau"e defecti!e red blood cell. -he cell" are "ha#ed li'e a cre"cent or "ic'le
occur" more commonly in #eo#le region" *here malaria i" or *a" common. there i" a "ur!i!al !alue in
carrying only a "ingle "ic'le.cell gene -ho"e *ith only one of the t*o allele" of the "ic'le.cell di"ea"e are
more re"i"tant to malaria, "ince the infe"tation of the malaria #la"modium i" halted by the "ic'ling of the
cell" *hich it infe"t".
"ic'le "ha#e body #roduce" abnormally "ha#ed red blood cell".
9b
"
"tiff : tend to accumulate in "mall ca#illary, 9b i" not efficient of tran"#orting o%ygen
#oly#e#tide chain encode by different gen, cau"e differ one ba"e only
No&ma l Mutant
nucleotide - ba"e i" re#laced by A ba"e
()A chain C - - C A -
tran"cri#t
mR)A 5 A A 5 0 A
tran"lation
code of amino acid glutamic !aline
ty#e of #rotein 93 normal 93 S
A change in a "ingle nucleotide from - to A in the ()A tem#late lead" to an abnormal #rotein.
Amino acid !aline re#lace" glutamic acid at a "ingle #o"ition in the #rotein
#ase inse&tions
Addition of 8 or a fe* ba"e #air" in the nucleotide "e,uence" in gene"
mutation of ba"e in"ertion ma'e cau"e frame "hift mutation
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No&ma Mutant
additional nucleotide in"ertion *ith ba"e 5
()A chain A5A 5-C --C A5A 55- C--
tran"cri#t
mR)A 0C0 CA5 AA5 0C0 CCA 5AA
tran"lation
code of amino acid Ser 5ln /y" Ser Pro 5lu
frame."hift ha##en
#ase 'eetions

/o"" of 8 or a fe* ba"e #air" in the nucleotide "e,uence" in gene"
mutation of ba"e deletion ma'e cau"e frame "hift mutation
No&ma Mutant
lo"t of - ba"e during re#lication of ()A
()A chain A5A 5-C --C A5A 5C- -C5
tran"cri#t
mR)A 0C0 CA5 AA5 0C0 C5A A5C
tran"lation
code of amino acid Ser 5ln /y" Ser Arg Ser
frame."hift ha##en
#ase in(e&sion
; ba"e #air" or more are in!erted in nucleotide "e,uence
No&ma Mutant
in!erted in nucleotide "e,uence
()A chain A5A 5-C --C A5A -5C --C
tran"cri#t
mR)A 0C0 CA5 AA5 0C0 AC5 AA5
tran"lation
code of amino acid Ser 5ln /y" Ser -hr /y"

F&ame)shi!t Mutations F&ame)shi!t Mutations
+n!ol!e in"ertion&deletion of a ba"e #air or more into the nucleotide" "e,uence of ()A
Many of the"e deletion"&in"ertion "tart in the middle of a codon
Shifting the reading frame by one or t*o ba"e"
<rame "hift mutation" cau"e the gene to be read in the *rong three ba"e grou#" (codon)
<rom the mutation #oint,
+t abru#t the coding "e,uence of amino acid.
Change" in codon" re"ult" in change" in amino acid"
(ifferent #oly#e#tide i" #roduced
$ffect = u"ually harmful to human
$.g.: Maor -hala"emia (mutant homo1ygote allele")
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C9ROMOSOMA/ M0-A-+O)
(efinition: Abnormalitie" = in chromo"omal "tructure (chromo"ome aberration) : change" in
chromo"ome number (aneu#loidy & eu#loidy)
Chromo"omal mutation" ta'e #lace *hen the number of chromo"ome" change" or *hen "tructural
change" occur in the chromo"ome"
Cla""ification chromo"omal mutation
i) Chromo"omal aberration ("tructural of chromo"omal change)
ii) Chromo"omal number alteration
. Aneu#loidy
. $u#loidy (#oly#loidy)
Chromo"ome" aberration
Change" in the chromo"ome" "tructure, are mo"t fre,uently formed during mito"i" or meio"i"
Rearrangement a certain segment @ parts of chromosome
4 ty#e" of chromo"omal aberration
i) -ran"location
ii) (eletion ("egmental deletion)
iii) +n!er"ion
i!) (u#lication
Analogy of frame-shift mutation
one sentences
CAN YO !Y CA" #OR $%R &ON
after insertion only one alphabet ' A at CA" in the sentence'
CAN YO !Y ACA "#O R$% R&O N
(e can)t rea* that sentence
after *elete only one (or*' C at CA" in the sentence
CAN YO !Y A"# OR$ %R& ON
(e can)t rea* that sentence
+peringatan analogi ini untu, ,efahaman saha-a ianya ti*a, boleh *iguna,an *alam peperi,saan
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-ran"location
-ran"location : in!ol!e" a region of a chromo"ome brea'ing off and reoining either the other end of the "ame
chromo"ome or another non.homologou" chromo"ome
e.g. Robert"onian tran"location
Robert"onian tran"location in!ol!e" brea'" at the e%treme" end" of the "hort arm" of t*o
nonhomologou" chromo"ome" (86, 84, 8>, ;8 and ;;)
)amed after the American in"ect genetici"t ?.3.Robert"on
Al"o called *hole.arm tran"location or centric.fu"ion tran"location
(eletion
Deletion : the lost of 1 segment containing 1 or more genes
?hen the chromo"ome brea'" at t*o #lace" and lead to the lo"" of the middle "egment
-he "egment lo"t may contain one or more gene"
-he remaining end of chromo"ome *ill oin again and become "horten
5enetic di"ea"e: Cri du chat "yndrome (u"ually mentally retarded and crie" li'e a cat me*ing)
/o"" of a "mall #art of the "hort arm of chromo"ome >
Cri du chat i" a rare "yndrome (8 in >@,@@@ li!e birth") cau"ed by a deletion on the "hort arm of
chromo"ome >.
-he name of thi" "yndrome i" <rench for Acry of the cat,A referring to the di"tincti!e cry of children *ith
thi" di"order.
-he cry i" cau"ed by abnormal laryn% de!elo#ment, *hich become" normal *ithin a fe* *ee'" of birth.
+nfant" *ith cri du chat ha!e lo* birth *eight and may ha!e re"#iratory #roblem".
Some #eo#le *ith thi" di"order ha!e a "hortened life"#an, but mo"t ha!e a normal life e%#ectancy.
?here doe" the abnormal chromo"ome > come fromB +n C@ #ercent of the ca"e", the chromo"ome
carrying the deletion come" from the fatherD" "#erm.
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+n!er"ion
Inversion : a region of a chromosome breaks off and rotates through 180 before rejoining the
chromosome
(u#lication
Duplication : a region of a chromosome becomes duplicated; an additional set of genes exists
?hen a "ingle locu" or a large #iece of a chromo"ome i" #re"ent more than once in the genome
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Alteration of chromo"ome" number
-y#e of the alteration of chromo"omal number
i. aneu#loidy
ii. eu#loidy & #oly#loidy
9uman "omatic cell" containing a number of chromo"ome" *hich i" not a multi#le of ;6 are called
aneuploi*s
Aneu*oi'+
Aneu*oi'+ i" a condition in *hich the number of chromo"ome" i" abnormal due to e%tra or mi""ing
chromo"ome", in other *ord", it i" a chromo"omal "tate *here the number of chromo"ome" i" not a
multi#le of the ha#loid "et.
)ormal di#loid "#ecie" ha!e ;n chromo"ome", *here n i" the number in the ha#loid "et.
Aneu#loid indi!idual" *ould ha!e ;n.8 chromo"ome" (mono"omy), ;nE8 chromo"ome" (tri"omy), or
"ome other "uch arrangement.
A change in the number of chromo"ome" can lead to a chromo"omal di"order. Aneu#loidy i" common in
cancerou" cell".
Aneu#loidy occur" during cell di!i"ion *hen the chromo"ome" do not "e#arate #ro#erly bet*een the t*o
cell"
-y#e of aneu#loidy 5enome "ituation
Mono"omy ;n . 8
-ri"omy ;n E 8
-etra"omy ;n E ;
,is-un"tion: chromo"ome" "e#arated to the o##o"ite #ole" during meio"i"
Non 'is-un"tion : !ailure of #air of chromo"ome to "e#arate and to mo!e to the o##o"ite #ole"
both "et" of chromo"ome" #a"" to the "ame #ole of the cell
Cau"e of aneu#loidy
)ondi"unction in Ana#ha"e + : ++
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Non'is-un"tion in Ana*hase I an' II (meiosis)
9alf the daughter cell" #roduced ha!e an e%tra chromo"ome" (nE8) *hil"t the other half ha!e a
chromo"ome mi""ing (n.8)
<u"ion gamete" bet*een chromo"ome (nE8) and normal gamete (n), #roduced embryo *ith
chromo"ome (;nE8) : -ri"omyF eg. (o*nG" "yndrome
<u"ion gamete" bet*een chromo"ome (n.8) and normal gamete (n), #roduced embryo *ith
chromo"ome (;n.8) : Mono"omyF eg. -urner Syndrome
Auto"omal abnormalitie"
Mono"omy ;8
-ri"omy ;8 (do*n "yndrome)
Monosom+
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Monosom+ i" the #re"ence of only one chromo"ome from a #air in a cellD" nucleu".
Mono"omy in human !ery rare, the maority embryo" donDt be "ur!i!e, <or li!e infant re#orted in human,
the only of mono"omy 8;
Mono"omy ;8
-he "yndrome i" generally lethal and only "e!eral ca"e" of li!ing ne*born infant" ha!e been re#orted,
mo"t of *hom die bet*een 6 *ee'" and ;@ month" of life but "ome "ur!i!e into childhood.
Sym#tom":
. Short di"tance bet*een eye"
. /arge ear"
. Contracted mu"cle
. /arge no"e *ith a broad ba"e
. cleft li# and&or #alate
. Short nec'
. Short thora%
. Small hand" and feet, o!erla##ing and&or fle%ed finger" and toe",
. hy#eracti!e refle%e" (ner!ou" "y"tem)
-ri"omy
T&isom+ i" a #re"ence genetic abnormality in *hich there are three co#ie", in"tead of the normal t*o,
chromo"ome" of a #articular numbered ty#e in an organi"m
A tri"omy i" a ty#e of aneu#loidy (an abnormal number of chromo"ome")
.uman t&isom+ can occur *ith any chromo"ome. Mo"t tri"omie", li'e mo"t other abnormalitie" in
chromo"ome number, re"ult in di"tincti!e and "eriou" birth defect". Mo"t tri"omie" re"ult in "#ontaneou"
abortionF the mo"t common ty#e" that "ur!i!e to birth in human" are:
. -ri"omy ;8 ((o*n "yndrome)
. -ri"omy 8C ($d*ard" "yndrome)
. -ri"omy 86 (Patau "yndrome)
. -ri"omy H
. -ri"omy C (?ar'any "yndrome ;)
. -ri"omy 8I i" the mo"t common tri"omy in human", occurring in more than 8J of #regnancie". -hi"
condition, ho*e!er, u"ually re"ult" in "#ontaneou" mi"carriage in the fir"t trime"ter
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A t&isom+ i" the
-hu" the #re"ence of an e%tra chromo"ome ;8 i" called tri"omy ;8
Sym#tom" (o*n "yndrome & tri"omy ;8
Short "tature. A child often gro*" "lo*ly and, a" an adult, i" "horter than a!erage.
?ea' mu"cle" (hy#otonia) throughout the body. A child may "eem to ha!e le"" "trength than other
children of the "ame age.
A "hort, *ide nec' *ith e%ce"" fat and "'in. 0"ually, thi" trait i" le"" ob!iou" a" the child get" older.
Short, "toc'y arm" and leg". Some children al"o ha!e a *ide "#ace bet*een the big toe and "econd
toe.
Re"#iratory #roblem"
?here doe" the e%tra chromo"ome come fromB
+n H@J of -ri"omy ;8 ca"e", the additional chromo"ome come" from the motherD" egg.
-hi" 'aryoty#e i" an e%am#le of Don !"ndrome (tri"omy ;8), the mo"t common numerical
abnormality found in ne*born". +t i" characteri1ed by an e%tra chromo"ome ;8 and the 'aryoty#e i"
*ritten a": /01231456. -he 'ey to the 'aryoty#e de"cri#tion i" a" follo*":
/0: the total number of chromo"ome" (4I i" normal).
23: the "e% chromo"ome" (male).
456: de"ignate" the e%tra chromo"ome a" a ;8.
Se% chromo"omal abnormalitie"
Aneuploi*y' abnormalitie" in the "e% chromo"ome number
)on di"unction during "#ermatogene"i" dan oogene"i"
e.g. Klinefelter "yndrome (4L,22M) and -urner "yndrome (4>,2O)
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)on di"unction during "#ermatogene"i"
+f non di"unction during ana#ha"e + : ++
"#erm *ill ha!e the abnormal "e% chromo"ome : 2M, 22 N MM
Abnormal "#erm % o!um (2)
Klinefelter "yndrome (22M)
Su#er male "yndrome (2MM)
62 female (metafemale, 222)
)on di"unction during Oogene"i"
+f non di"unction ha##ened
Some o!um might not carry any chromo"ome 2 : "ome other" might carry ; chromo"ome 2
Abnormal o!um (O) % "#erm
-urner "yndrome (2O)
MO : dead
Abnormal o!um (22) % "#erm
Klinefelter "yndrome (22M)
62 female
Klinefelter "yndrome (4L,22M)

KlinefelterD" Syndrome i" a genetic di"order that ha##en" in 8 in e!ery >@@ to 8@@@ male birth".
+n"tead of the normal 2M chromo"ome", the"e indi!idual" ha!e and e%tra 2 chromo"ome ma'ing them
22M.
Male" *ith KlinefelterD" "yndrome ha!e t*o 2 chromo"ome" (4L.22M), -he 2.chromo"ome" carry
gene" in term" of de!elo#ment of te"ticle", "e% hormone #roduction and #hy"ical "e% de!elo#ment in
general a" *ell a" to a certain e%tent al"o height gro*th.
+t i" named after (r. 9arry Klinefelter, a medical re"earcher at Ma""achu"ett" 5eneral 9o"#ital, 3o"ton,
Ma""achu"ett", *ho fir"t de"cribed thi" condition in 8H4;.
Sym#tom"
. delayed "#eech
. "en"ory integration difficultie", including "en"iti!ity to noi"e
. hy#otonia or lo* mu"cle tone
. auditory #roce""ing #roblem"
. language.ba"ed learning di"abilitie", including reading difficultie"
. an%iety
. de#re""ion
. gynecoma"tia or "*elling of brea"t ti""ue during #uberty
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. <emini"ed male ("oft !oice
. Sterile male ("mall te"ti"), failed to #roduce "#erm
. long hand and leg
-urner "yndrome (4>,2O)
-urner "yndrome re"ult" from a chromo"omal abnormality in *hich a female infant i" born *ith only one
2 chromo"ome (in"tead of the u"ual t*o) or i" mi""ing #art of one 2 chromo"ome.
Sym#tom"
. "hort "tature
. A*ebbingA of the "'in of the nec' (e%tra fold" of "'in e%tending from the to#" of the "houlder" to the
"ide" of the nec')
. a lo* hairline at the bac' of the head
. lo*."et ear"
. abnormal eye feature", including droo#ing of the eyelid"
. abnormal bone de!elo#ment, e"#ecially the bone" of the hand" and elbo*"
. a lac' of brea"t de!elo#ment at the e%#ected age (u"ually by age 86)
. an ab"ence of men"truation (amenorrhea)
. a larger than u"ual number of mole" on the "'in
A$no&ma Phenot+*e
7ine!ete& S+n'&ome (223) : 5n46 (T&isom+)
Sterile male ("mall te"ti"), failed to #roduce "#erm
<emini"ed male ("oft !oice) : big brea"t, long hand and leg
)on di"unction during oogene"i"
Tu&ne& S+n'&ome (2O) : 5n)6 (Monosom+)
Sterile female (failed to o!ulate)
Small brea"t : unde!elo#ed o!ary
d*arf, deaf, abnormal heart : lo* +O
$u#loidy & Poly#loidy
cell of organi"m that ha" an e%act multi#le of the ha#loid number (n) of chromo"ome" in a nucleu".
5amete" fu"ion *ill #roduce cell *hich ha!e more than ; "et of chromo"ome, for e%am#le: di#loid (;n),
tri#loid (6n), and tetra#loid (4n) nuclei or cell are eu#loid
Occurred *hen a "et of chromo"ome did not "e#arate during gametogene"i"
Common in #lant" than in animal", cau"e gamete not occur in animal, *hile in #lant can #roduce
!egetati!e #ro#agate.
-ri#loid (6n) occur" *hen
i) a gamete (;n) occur non di"unction fu"ed *ith a normal gamete (n)
5amete A % AA (non di"unction gamete)
indi!idual of tri#loid AAA

ii) chromo"ome" di"able to "egregate during meio"i" to #roduce di#loid gamete
iii) gamete from tetra#loid organi"m (4n) fu"ed *ith di#loid organi"m gamete (;n).
e.g. #lant tri#loid i" a banana, lemon, ro"e, *atermelon ("eedle"") and cry"anthemum
-etra#loid #lant" can be #roduced by :
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8) Somatic du#lication of chromo"ome number
. du#lication of chromo"ome at callu" (ti#)
.
origin #lant : AA (;n)
((u#licate)

tetra#loid #lant AAAA (4n)

;) <u"ion of t*o di#loid gamete"
P : AA (;n) AA (;n)
5 : AA AA
<+: AAAA
; ty#e" of #oly#loidy
. Auto#oly#loidy
. Allo#oly#loidy
Auto*o+*oi'+ :

+" an indi!idual that ha" more than t*o chromo"ome "et", all deri!ed from a "ingle "#ecie"
-he chromo"ome" "et are homologou" *ith the #arent cell
+m#ortance in economic !alue *hich auto#oly#loid #lant" #roduce flo*er" and fruit" bigger than normal
di#loid #lant"
+n!ol!e #arent cell from one "#ecie" mean homologou" chromo"ome
P : AA (;n) AA (;n)
5 : AA % AA

<+: AAAA
Ao*o+*oi'+
A #oly#loid re"ulting from ; different "#ecie" (hybridi1ation) interbreeding and combining their
chromo"ome"
-he chromo"ome "et" are different to #arental cell mean non homologou" chromo"ome "et" in!ol!e
<8 hybrid" #roduced from different "#ecie" are u"ually "terile (ha#loid "et of chromo"ome from one
"#ecie" cannot #air during meio"i" *ith the ha#loid "et from the other "#ecie")
Chromo"ome number in a "terile hybrid become" doubled and #roduce" fertile hybrid" ("yna#"i" and
"egregation can occur and !iable gamete" can be #roduced)
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+m#ortance in #roducing ne* "#ecie"
e.g. #lant (*heat)
Triticum diccoccum (;n 7 4% 7 ;C) % Aegilops squarrosa (;n 7 ;% 7 84)
-etra#loid #lant

Triticum vulgare (;n 7 I% 7 4;)
9e%a#loid #lant
P : AA 33
5amete A % 3
9ybrid ( "terile ) A3
du#lication
AA33
5amete, ;n 7 ;% ( fertile ) A3
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Spartina anglica i" a "#e"ie" of cordgra"", +t i" an allo#oly#loid "#e"ie" deri!ed from the hybrid Spartina
x townsendii
P Spartina maritima ("mall cordgra"") % Spartina alterniflora ("mooth cordgra"")
9ybrid Spartina x townsendii
dublication
Spartina anglica
Retold by
Amran Md Said
Matriculation College of Pahang.
-he end.