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8/20/2019 Flash Notes Genetics
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GENETICS | 1
Gene/ Protein/Oncogene/
Chromosome
Disease Things to remember
α SYNUCLEIN Proteinand
PARKIN GeneMutation
PINK 1 Gene
Alpha Synucleinopathy
u!enile "n#etPar$in#on%# &i#ea#e
• Ma#$'li$e (ace• S)all hand*ritin+
,)icro+raphia-.de)entia
• &ecrea#ed
/lin$in+• 0ypophonia• Shuin+ +ait• 2all3 the MC
pro/le) inPar$in#on%#
A##ociated *ith3• Parkinson’s di#ea#e ,a4$4a4
Paralysis Agitans-e4+4 Michael 42o5. Muha))ad Ali.2reddie Roach2our )otor #y)pto)#3
1. Unilateral Resting tremors(“pill-rolling” of hands)
2. Cogwheel!eadpipe rigidity ". #rady$inesia A$inesia%. Post&ral insta'ility (“stooped”
post&re)
Lack of Dopamine in par#co)pacta neuron# o( the Su/#tantia
Ni+ra 6yro#ine3 the a)ino acid precur#or o( dopa)ine
Levodopa + Carbidopa. Sele+iline.Ra#a+ilineC"M6 inhi/itor# ,entacapone.tolcapone-Anticholiner+ic# ,trihe5yphenidyl./en7tropine-A)antadine
0aloperidol3 the MC dru+ that cau#e#
Par$in#oni#) 80aldol #hue9,Antidote3 :iperiden,A$ineton--
Accu)ulation o( Lewy Bodies Multiple Sy#te) Atrophy ,MSA-
A&IN"PEC6IN An anti'in;a))atorycyto$ine
• Produced e5clu#i!ely /yadipocyte#
• Enhance# insulinsensitivity . and inhi/it#)any #tep# in in;a))ation
•
Reduced in Meta/olicSyndro)e. hence. cau#in+the in#ulin re#i#tance
ALK protein Anaplasti lymphoma
$inaset!"#$
Anapla#tic lar+e cell< nullcell ly)pho)a
• :one )arro* in=ltration o()onoclonal B cell#> ,for then&llnon-* + non-#-
• S)ud+e cell# ,/a#$et cell#-• *< imm&nopositi,ity to C"
a.$.a. /i-1
• Clu#terin. another )ar$er
that *ould di?erentiate (ro)0od+$in%#• 0a!e a +ol+i'#tainin+ pattern
Anti'CEN6R"MERE. 6he li)ited cutaneou# CRES6 Syndro)e ,the acrony)-
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GENETICS | *
6hy)o)a3 the MC a##ociated tu)or*ith MG&"C3 Pyrido#ti+)ineAlt43 Neo#ti+)ine
Anti'ri/o#o)al P A/ P#ycho#i# F to CNSlupu#
Anti'Ro A/ Neonatal Lupu# Con+enital heart /loc$
Anti'SCL' Anti/odya4$4a4
Anti'topoi#o)era#e I
Anti'nuclear anti/odie#3Anti'RNA poly)era#e I.
II. and III
Anti'UJ RNP
&i?u#e Sy#te)icScleroder)a
• "!erproduced 6ran#(or)in+Gro*th 2actor
• CRES6 #yndro)e• -A2& ,+a#tric antral !a#cular
ecta#ia- al#o $no*n a#8watermelon stomah”
•
Mali+nant hyperten#ion• May /e cau#ed /y
Bleomycin and 'aane
• 6he Anti'UJ RNP i# al#o hi+hly#peci=c (or SSc *ith)u#culo#$eletal. +a#tric andpul)onary in!ol!e)ent
• Sclerede)a ,sleredemaad<or&m of #&sh$e-'predo)inantly in children>painle## ede)atou#induration in!ol!in+ the (ace.#calp. nec$. trun$. andpro5i)al portion# o( thee5tre)itie#
• Patient# *ith in#ulin'dependent dia/ete# )ellitu#)ay de!elop di+ital #clero#i#and contracture# , prayerhand deformity -
Anti'o 1 In;a))atory Myopathy
Antipho#pholipid A/ APAS,anti'pho#pholipid
anti/ody #yndro)e-
Clottin+ predi#po#itionRepeated (etal lo## 6hro)/ocytopenia
Anti'U1 RNP Mi5ed Connecti!e 6i##ue&i#ea#e
8o!erlap #yndro)e9
• In O'1Q o( patient#• 0a# (eature# o( So+ren%#
#yndro)e• 0a# (eature# o( Scleroder)a
,CRES6 #yndro)e-• 0a# (eature# o( SLE3 )alar
ra#h. photo#en#iti!ity. di#coidle#ion#. alopecia. pain(ul oralulcer#
• Pul)onary arterial
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GENETICS | +
hyperten#ion i# the )o#tco))on cau#e o( death
APC Gene,Adeno)atou#Polypo#i# Coli-
,ami%ia% 'denomatousPo%$-osis
a..a. Gardner0s
s$ndrome,)utation# in APC +ene-
Co%orecta% Cancer,inacti!ation o( APC
+ene-remem'er 8-9U
APC +ene i# located in the lon+ ,D-ar) o( Chro)o#o)e 3#4!56
Allelic loss3 production o( an APCprotein that i# a/nor)ally #hort andnon(unctional
#u/#titution o( the a)ino acid lycine(or isoleucine at po#ition 1J inthe APC protein
beta.catenin. i# controlled /y theAPC protein> pre!ent# cello!er+ro*th
AP"LIP"PR"6EIN EH,AP"EH-
Pre'Senilin IPre'Senilin II
Al7hei)er%# &i#ea#e • Neuro=/rillary tan+le#co)po#ed o( a/nor)allypho#phorylated 6au protein
• A)yloid protein#> located inChro)o#o)e F1 #enileplaDue#
,N"6E3 co))on (actor /et*een A&and &o*n%# #yndro)e3 chro)o#o)eF1-
• 0ippoca)pal atrophy• ,- 0irano /odie# in the
neuron#• A!era+e duration3 '1 year#• End #ta+e3 Pt *ill /e ri+id.
)ute. incontinent. /edridden• 6ACRINE3 a )edicine (or A&
/ut not u#ed any)ore• &"C3 Anti'
Aceylcholine#tera#e Inhi/itor,to pre!ent (urther/rea$do*n o( the 8already'depleted9 le!el# o( Ach-
A6ATIN'1 Gene Spinocere/ellar ata5ia
Machado o#eph &i#ea#e
SCA 6ype 13 C A - repeat @p0yper)etric #accade#Slo* #accade#Upper )otor neuron
SCA 6ype F3 C A - repeat 1FD&i)ini#hed !elocity #accade#Are;e5ia
SCA 6ypeJ3 C A - repeat 1HDGa7e e!o$ed ny#ta+)u#Slo* #accade#Upper )otor neuron
A6M +ene Inacti!ated in 'taiate%angiectasia
Encode# a $ina#e e##ential (or pJacti!ityCharacteri7ed /y hyper#en#iti!ity to
http://en.wikipedia.org/wiki/Amino_acidhttp://en.wikipedia.org/wiki/Isoleucinehttp://en.wikipedia.org/wiki/Isoleucinehttp://en.wikipedia.org/wiki/Isoleucinehttp://en.wikipedia.org/wiki/Beta-cateninhttp://en.wikipedia.org/wiki/Amino_acidhttp://en.wikipedia.org/wiki/Isoleucinehttp://en.wikipedia.org/wiki/Beta-catenin
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GENETICS | 2
5ray# and predi#po#ition toly)pho)a#
A!idin /loc$# the co'en7y)e:I"6IN3 Bit4:
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GENETICS | 3
(eed/ac$ #i+nal# that stop eatin*be(avior
:RCA1 ,1D-:RCAF ,1JD-,onco+ene#-
"!arian CA:rea#t CA
ReDuired (or pJ acti!ity
Char+a?%# rule 131 ratio o( Purine# andPyri)idine#
'denine al*ay# pair# *ithThy)ine 8cat%# )eo*9> cat%#eye#' epcanthal (oldchro)o#o)e p deletion#yndro)e auto#o)al rece##i!e,- Chloride #*eat te#t ,X))ol
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GENETICS | 6
Ata5ia. ny#ta+)u#.$ypho#colio#i#. pe# ca!u#,hi+h arched (oot-Spinal cord /eco)e#thinner de)yelinationMental (unction# are not
a?ected
6reat)ent3 I&E:EN"NE
-rotein ,ratain# an iron /indin+protein re#pon#i/le (or (or)in+ iron'#ulphur clu#ter#
(rata5in de=ciency i# )itochondrialiron o!erload *hich can cau#eda)a+e to )any protein#
E-anded G ' ' triple repeat#>auto#o)al rece##i!e
C0R"M"S"ME 1 Re(#u)%# di#ea#e Phytanoyl Co'A de=ciency,or Phytannic acid-
C0R"M"S"ME 1J Patau Syndro)e 6ri#o)y 1J 9:;5"Li 2rau)eni Syndro)e
Lon* arm"5:4""!arian cancer
Cana!an%# di#ea#e
Ca(Z au Lait Spot#Li#ch nodule# on iri#Neuro=/ro)ato#i# I
6pJ 6u)or Suppre##or GeneGuardian o( the Geno)eSe!eral cancer# are in!ol!ed
0ereditary cancer> +er)line)utation# o( :RCA tu)or #uppre##or
+ene
&e=ciency o( a#partocycla#e ora)inocycla#e F le!el# o( N'acetyla#partate are chronically ele!ated
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GENETICS | 7
Pro+re##i!e de)yelination o( ner!ecell# in the /rain death /e(ore a+eH
C0R"M"S"ME 1 Ed*ard# Syndro)e 6ri#o)y 1
H.TT.1
• Pro)inent occiput. MR.)icro+nathia
• Lo* #et ear#. #hort nec$• Clenched =#t. o!erlappin+
=n+er#• 0eart and renal
)al(or)ation#• Li)ited hip a/duction• Roc$er'/otto) (eet
C0R"M"S"ME F1 &o*n%# Syndro)e 6ri#o)y F1 ,H.TY.F1-
• 2lat (acie#. o/liDue palpe/ral=##ure. epicanthic (old#.simian hand reases
• Con+4 heart di#ea#e• Recurrent in(ection#• Acute ly)pho/la#tic leu$e)ia
,[ri#$-• Pre)ature Al7hei)er%#
di#ea#e• &uodenal atre#ia
Colla+en 6he )o#t a/undantprotein in the /ody>
0ydro5ylation o( Glycine.Proline into
0ydro5yproline and0ydro5yly#ine
BI6AMIN C cro## lin$# colla+en>#cur!y i# due to it# de=ciency
6ropocolla+en3 J polypeptide chain#
c'UN +ene Proto'onco+ene I)portance3A +ro*th'pro)otin+ +ene 6ran#cription re+ulationNe+ati!e re+ulation o( &NA /indin+
C'KI6 onco+ene Ga#tro'inte#tinal Stro)al 6u)or#,GIS6#-
6u)or# are o( )e#oder)al,inter#titial cell# o( Caal-
• :leedin+ or GI o/#truction•
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GENETICS | 18
#yntha#e
CYPF1A F1'0ydro5yla#ede=ciency
Mutation# in thi# +ene cau#e#defeti,e on,ersion o( pro+e#teroneto 11'deo5ycortico#terone
14 Salt'*a#tin+ #yndro)e3
co)plete de=ciency o( F1'hydro5yla#eF4 Si)ple !irili7in+ adreno+enital
#yndro)e *ithout #alt*a#tin+
J4 Non'cla##ic ,late on#et-adrenal !irili#)3 partial F1'hydro5yla#e de=ciency acne. hir#uti#). )en#trualirre+ularitie#
&NA 0ELICASE
)utation
erner #yndro)e • Pre)ature a+in+• accelerated accu)ulation o(
chro)o#o)al da)a+e• )i)ic# the inury that
nor)ally acco)panie# a+in+
&YNEIN de(ect Pri)ary Ciliary&y#$ine#ia
Karta+ener%# #yndro)e 6riad3
14 Situ# in!ertu# ,de5trocardia-F4 Chronic #inu#iti#J4 :ronchiecta#i#
&YS6R"P0IN,the :IG +ene-
&uchenne Mu#cular&y#trophy
• MC (or) o( childhood)u#cular dy#trophy
• ,- Go*er%# Si+n• P#eudohypertrophy o( the cal( • 2ra)e#hi(t )utation in O@Q• Ne* )utation in JQ
&Y6J Gene T&PSe5'lin$ed &y#tonia o(
Panay
2ound in Panay I#land Philippine#,L1BA-/
• uniDue to adult 2ilipino )en
• pronounced atrophy o( thecaudate and putamen
,u#t li$e 0untin+ton%#di#ea#e-
Er/':F ,0erF
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GENETICS | 1
and tran#criptional#uppre##ion
• A?ected )ale#3 pro+re##i!eneurode+eneration. #e!ereMR. enlar+ed te#te#
• A?ected (e)ale3 pre)atureo!arian (ailure
2RA6ATIN Gene(a mitohondrial
protein)
2riedreich%# Ata5ia • e5pan#ion o( an intronic - A A triplet repeat>
• are;e5ia. up+oin+ toe#.!i/ration and po#ition #en#ede=cit#. #colio#i#. cardiomyopat(y . ha))ertoe#
• )debenone. a (ree'radical#ca!en+er. )ay i)pro!e)yocardial hypertrophy in
2A• iron chelator# and antio5idant
dru+# can increa#e)yocardial inury in 2A
G0RELIN the hun+er hor)one increa#e# the appetite and (a!or# theaccu)ulation o( a/do)inal (at#produced )ainly /y Paline : aple syr&p&rine disease
• Mi##en#e Mutation• 0e)olytic cri#i# ' ane)ia• SeDue#tration cri#i# ' #pleen• Par!o!iru# :1O tri++er#
Apla#tic cri#i#• :ene=t (ro) routine 2lu
!accine• Sic$le #hape +i!e# re#i#tance
to Malaria•
indi+enou# inha/itant#o( Su/'Saharan A(rica
GRAN^YME : • A C6L'deri!ed #erine protea#e
http://en.wikipedia.org/wiki/Indigenous_peopleshttp://en.wikipedia.org/wiki/Sub-Saharan_Africahttp://en.wikipedia.org/wiki/Indigenous_peopleshttp://en.wikipedia.org/wiki/Sub-Saharan_Africa
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GENETICS | 1!
Acti!ate# )ultiple ca#pa#e#. there/y.directly inducin+ the e?ector pha#eo( apopto#i#
0ER'F onco+ene :rea#t carcino)a • Indicate# a poor pro+no#i# i(,-
• Can /e treated *ith tar+etedtherapy. #uch a# 6ereptin
0i#tidine 6he /u?erin+ capacity o( he)o+lo/ini# due to thi# a)ino acid re#idue
0LA :F An$ylo#in+ Spondyliti#(a.$.a. arie ?tr&mpell
disease #ehterew7s disease)
Reiter%# Syndro)e
:ehcet%# #yndro)e
MC Serone+ati!e Spondylo'arthropathy“'am'oo spine appearane” ,- Scho/er 6e#t3 li)itation o(lu)/ar ;e5ion,- Sacroiliti# on TRay
'riad 314 In;a))atory ,reacti!e-
arthriti#F4 Conuncti!iti# ,u!eiti#-J4 Urethriti# ,in )en- or
Cer!iciti# ,in *o)en-
• Keratoder)a /lenorrha+ica)o#t co))on tri++er# are inte#tinal
in(ection# *ith Salmonella ;S(i*ella or Campylobacter and#e5ually tran#)itted in(ection#*ith C(lamydiatrac(omatis or 7eisseria*onorr(eae
• "ral and +enital ulcer#• U,eitis ( 6!A #2@ )
• Pro+re##i!e optic atrophy• Intracranial hyperten#ion *ith
papillede)a
0LA :H F1'hydro5yla#e&e=ciency
0LA &RF SLE
0LA &RJ • Pri)ary So+ren%##yndro)e
• &ia/ete# Mellitu#
type 1• SLE• Po#t+onococcal
arthriti#
Sicca #yndro)eSchir)er%# te#t
http://en.wikipedia.org/wiki/Salmonellahttp://en.wikipedia.org/wiki/Shigellahttp://en.wikipedia.org/wiki/Campylobacterhttp://en.wikipedia.org/wiki/Chlamydia_trachomatishttp://en.wikipedia.org/wiki/Chlamydia_trachomatishttp://en.wikipedia.org/wiki/Chlamydia_trachomatishttp://en.wikipedia.org/wiki/Neisseria_gonorrheaehttp://en.wikipedia.org/wiki/Neisseria_gonorrheaehttp://en.wikipedia.org/wiki/Salmonellahttp://en.wikipedia.org/wiki/Shigellahttp://en.wikipedia.org/wiki/Campylobacterhttp://en.wikipedia.org/wiki/Chlamydia_trachomatishttp://en.wikipedia.org/wiki/Chlamydia_trachomatishttp://en.wikipedia.org/wiki/Neisseria_gonorrheaehttp://en.wikipedia.org/wiki/Neisseria_gonorrheae
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GENETICS | 1*
"9' DR*,&R 1_H1-[[[ri#$
,&R 1_HH-,&R 1_11-
%(eumatoid @actor
in @@Q o( P5
Anti.CyclicCitrullinated Peptide
,anti'CCP-OQ #peci=cityIndicate# poor
pro+no#i#
Rheumatoid 'rthritis
6N2'α3 in;a))ation.(e!er. /one and cartila+ere#oprtion
IL'1α3 attac$# thy)o#ite#and neutrophil#IL'13 attac$# :6 cell#.and ti##ue cell#IL'@3 di?erentiation and/one re#orption
Rheu)atoid nodule
CA& and carotidathero#clero#i#3 MCcau#e o( death in RA p5
Per#i#tent in;a))atory #yno!iti#• MC (or) o( C0R"NIC arthriti#• Sy))etric polyarthriti#.
re#ult# in oint da)a+e• Sy#te)ic di#ea#e *ith
e5traarticular )5 ,XJoint#->
#
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GENETICS | 1+
K'RAS Gene Colorectal CAPancreatic CA
Lun+ CANoonan #yndro)e
Cardio'(acio'cutaneou##yndro)e
MC #ite3 Si*moid colon
An onco+ene that i# a G'PR"6EIN
A )olecular ono #*itch
LEP6IN )n(ibits appetite /y counteractin+the e?ect# o( neuropeptide 3 apotent (eedin+ #ti)ulant #ecreted /ythe cell# in the +ut and in thehypothala)u#
• Reduced in Meta/olicSyndro)e
Microphthal)iaa##ociated tran#cription
(actor ,MI62- +ene
6iet7% #yndro)e &ea(ne##Al/ini#)Leuci#)(defets in all types s$in pigmentsBnot &st melanin)
Mirror i)a+e# Enantio)er# ,in /ioche)-Reed'Stern/er+ cell# ,in patho-
Moti( 0eli5 to heli5^inc =n+er
Leucine 7ipper
SeDuence pattern o( nucleotide# in a&NA #eDuence or a)ino acid# in aprotein
NAGA +ene Schindler di#ea#e(a.$.a. /anDa$i disease)
α'N'acetyl+alacto#a)inida#ede=ciency
I4 6ype I ,In(antile-3 )ore#e!ere. *ith neurolo+ical andneuro)u#cular #y)pto)#
II4 6ype II ,Adult-3 )ilder>an+io$erato)a#. )ildintellectual i)pair)ent
III4 6ype III ,Inter)ediate-3#ei7ure#. MR. auti#tic'li$e/eha!ior. delayed #peech
NRAM Genetic protein,Natural Re#i#tance
A##ociatedMacropha+e-
AI&SMyco/acteriu) A!iu) Intracellulare(E!ady Findermere syndromeE)
collar#tud a/#ce##
P'1@ Pancreatic CA • Bery #peci=c (or pancreaticCA
• 6he )o#t (reDuentlyinacti!ated tu)or #uppre##or+ene
P'J 6u)or Suppre##orGene
9i:,raumeni S$ndrome#e!eral $ind# o(
CA7C&% are in!ol!ed>o(ten appear# at a yo&ng
-uardian of t(e -enome
• 6PJ a##i#t# in repair orde#truction o( /ad orda)a+ed &NA
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GENETICS | 13
Ra)achandran Plot 6he an+le# o( the t*o )o#t co))ontype# o( #econdary #tructure. α'heli5and #heet. (all *ithin the lo*er andupper le(t'hand Duadrant#
R/ 1JD,onco+ene- Retino/la#to)a
"#teo#arco)a
2le5ner'inter#teiner p#eudoro#ette#
8#un/ur#t pattern9 on Tray
S'1 protein A# tu)or )ar$er (or3• Mali+nant
Melano)a• Mali+nant
Peripheral Ner!eSheath tu)or#
• Sch*anno)a•
0i#tiocyto)a• Clear Cell
Sarco)a
)c3 Super=cial Spreadin+ type or thene#ted patternDysplastic nevus3 precur#or o(MMelano)a
S Pha#e 6he pha#e i# the cell cycle *hen &NAunder+oe# replication
Shine'&al+arnoSeDuence
• Ri'osomal 'inding site in the
mR3A +enerally locatedup#trea) o( the #tart codon<initiatin+ codon3 AUG
• 0elp# recruit the ri/o#o)e# tothe )RNA to initiate protein#ynthe#i# /y ali+nin+ it *iththe #tart codon
• 2ound in pro$aryotes• Core &NA #eDuence3
+0T'T'''!0• ;o&a Se
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GENETICS | 16
he)oly#i#• ,- 6owell-Holly 'odies
Ane)ia. hyper/iliru/ine)ia.#pleno)e+aly
S6K11 +ene on
Chro)o#o)e 1O,)utation-
Peut7'e+her# #yndro)e
(a.$.a. hereditary intestinal polysposis
syndrome)
:eni+n ha)arto)atou# polyp# o( the
GI6• 0yperpi+)ented )acule#
around the lip# and oral)uco#a
"ral =ndin+# are #a)e *ithAddi#on%# di#ea#e and McCuneAl/ri+ht
6a)) 0or#(all protein Uro)odulinProtein in the $idney tu/ule#
6A6A :o5 a4$4a4 Gold/er+'0o+ne##:o5
A &NA #eDuence ,ci# re+ulatoryele)ent- (ound in the pro)oterre+ion o( +ene# in eu$aryote#
6AU Protein 6aupathy
Al7hei)er%# di#ea#e
?yperp(osp(orylation *ill lead to#el('a##e)/ly o( tan+le# o( pairedhelical =la)ent# and #trai+ht=la)ent#
at#on and Cric$
)odel o( &NA
!*=3 one co)plete turn
or heli5 pitch o( theat#on and Cric$
6eliase3 the en7y)ethat *ill un*ind the &NAheli5
&ecri/e# the &NA a# (ollo*in+3
• :a#e pairin+• 0elical• Ri+ht'handed• Co)pli)entary #trand#• Anti'parallel #trand#• Su+ar'pho#phate /ac$/one
out#ide and /a#e# #tac$edin#ide
• 6*i#ted ladder #tructure
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GENETICS | *
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