BIOL 3301 - Genetics Ch2C - Human Genetics St

8/18/2019 BIOL 3301 - Genetics Ch2C - Human Genetics St

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Human Genetics

• Single gene defects

• Chromosomal disorders

• Multifactorial (quantitative) traits


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Single Gene Disorders

• A single gene disorder is one that isdetermined by a

and thes!ecific allele on one or both members ofa chromosome !air"

• Single gene defects are rare# $ith a

frequency of less than "


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Autosomal Dominant

Huntington syndrome

+rogeria+olydactyly


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TraitChromosome forGene Location

DominantPhenotype

PossibleDominantGenotypes

RecessivePhenotype

RecessiveGenotype

color of iris , not blue -- or -e blue ee

widow'speak

. !ea* ++ or +! no !ea* !!

cheekdimples

/ dim!les DD or Dd not dim!les dd

face

freckles 0 frec*les 11 or 1f no frec*les ff

mid-digitalhair

23 hair HH or Hh no hair hh

itchhiker!s th"mb

24 straight %% or %t curved tt

all"#

length$toes% ,3 long ,nd toe 55 or 5b

long big toe or 6

to ,nd toe bb

&ar lobes ,2 free 77 or 7l attached ll

Tong"erolling

,, ability 88 or 8r no ability rr

Cleft chin

29 cleft :: or :y no cleft yy


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%ongue 8olling

• A sim!le t$oallele character# $ith the allelefor rolling (usually given the symbol % or 8)

over the allele

for nonrolling (t or r)"


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Cleft Chin

• Se!arate chee* and chin dim!le genes• Dim!les on chromosome / and cleft chin on

chromosome 29

• Cleft chin a classic e;am!le of • %he a!!earance of a feature li*e a cleft chin is

de!endent on t$o genes# the and the cleft gene itself"

• %here is a gene (M )that $hen dominant# doesn


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Dominant 7ethal Genes

• S!ontaneous dominant mutation

' normal height ' aa ' D$arfs ' Aa

' AA ' lethal

' affects less than ,33#333 !eo!le in the =S!o!ulation


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Achondro!lasia

• Autosomal dominant mutation

• Gene on chromosome . (.!29">)

• 1G18> gene fibroblast gro$th factorrece!tor gene

•

• Severely shortened bones


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Achondro!lasia

• > out of . cases ' ne$ mutation# s!ontaneous

• ?ncrease $ith age (@>/ years old)

• -;clusively inherited

• 00 cases ' t$o mutations of 1G18> ' G22>BA ' glycine to arginine in !rotein 0B

' G22>BC ' 2

• Missence mutation 7ys9/3Met in tyrosinase*inase ' severe achondro!lasia $ithdevelo!mental delay


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+rogeria

• "tchinson-Gilford Progeria yndrome is ane;tremely rare genetic disease that acceleratesthe aging !rocess to about seven times thenormal rate"

• 5ecause of this accelerated aging# a child of tenyears $ill have similar res!iratory#cardiovascular# and arthritic conditions that a 43yearold $ould have"

• +rogeria affects bet$een (estimatedactual) and 2 in B million (re!orted) children#


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Huntington Disease

• Chromosome .

• Mutation of the gene causes Huntingtonchorea# #lethal in later age (2&23#333)

• Deletion of the gene ' olfHirschhornsyndrome# carriers die young


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Huntington Disease

• Gene contain CAG re!eat ' (CAG)n too*

2, years to determine

•n>/# you are fine• =sually 232/ re!eats

• n@>0 ' Huntington chorea# slo$

deterioration of the intellect# muscularactivity# etc" Can last 2/,/ years"


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Huntington Disease

• Gene codes for !rotein huntingtin

• Another !rotein# HA+2# im!ortant for normalfunctioning of hy!othalamus# by lin*ing to

trans!ort !roteins# !rotecting them and ensuringnormal gro$th of neurites

• HA+2 needs to be !hos!horylated to be active

• Abnormal# or mutant huntingtin !revent!hos!orylation of HA+2

htt!&EE$$$"yourgenesyourhealth"orgE


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Autosomal 8ecessive


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Trait Chromosome for Gene LocationGenotype$normal%

skin cancer 2 Cc

cystic fibrosis 4 Fq

albinism 22 Aa

#eroderma pigmentosa 2/ ;

l"ng cancer > n

P() $phenylketon"ria% 2, Gg

*"sc"lar Dystrophy se; chromosome Mm (girls only)


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Albinism

• 2&>>#333 Caucasians

• 2&,B#333 African American in =S

• Affects a gene for # an enymeused in conversion of tyrosine to DI+A#from $hich the bro$n !igment melanin

derives• %here are at least of

albinism


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Albinism

• %$o main ty!es& ' %y!e 2 '

#

autosomal gene(s)# oculocutaneous (ICA)J$hite or !in* s*in# hair# iris color# vision!roblems

' %y!e , (IA) ' ocular albinism# affects only

# no melanin in retina#• IA2 ' genetic defect in G+82.> gene#

chromosome


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Albinism

• ICA ' genetic defect of tyrosinase enyme inconverting tyrosinase to melanin& ' ICA2A '

' ICA25 ' tyrosinase is minimally active# some color ' ICA> ' genetic defect in %:8+2

' ICA. ' genetic defect in S7C./ !rotein

' Combination of eight genes ' Hermans*y+udla*

syndrome ' albinism# bleeding !roblems# bruising#lungs# bo$el diseases


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Albinism

• Any forms of albinism have some of thefollo$ing !ossible sym!toms& ' 8a!id eye movements (nystagmus)

' Strabismus (eyes not trac*ing !ro!erly) ' +hoto!hobia (avoidance of light because of

discomfort)

'Decreased visual acuity or even functionalblindness


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The TYRP1 gene is located on the short (p) arm of chromosome 9

at position 23.More precisely, the TYRP1 gene is located from

ase pair 12,!"3,##" to ase pair 12,$%%,2&$ on chromosome 9.


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'MM http**+++.nci.nlm.nih.go*entre-*dispomim.cgiid/3%%&%%

The 0PR1#3 gene is located on the short (p) arm ofthe chromosome at position 22.3. More precisely, the 0PR1#3

gene is located from ase pair 9,!&3,#&3 to ase pair 9,!93,91!

on the chromosome.


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-ye color

• ?n humans involved in eye color are *no$n"

• %hey e;!lain ty!ical !atterns ofinheritance of bro$n# green# and blue eyecolors"

• Grey eye color# Hael eye color# andmulti!le shades of blue# bro$n# green# andgrey are not e;!lained"


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-ye Color

• %he *no$n Human -ye color genes are& ' -:C72 (also called gey)# the

# located on chromosome20 (though there is also evidence that another gene $ith similaractivity e;ists but is not on chromosome 20)"

' -:C7, (also called bey2)# the central bro$n eye color gene#!ossibly located on chromosome 2/"

' -:C7> (also called bey,)# the eyecolor gene located on chromosome 2/"

• -:C7> !robably involves mutations in the regulatoryregion Kust before the ICA, gene ($hich !roduces a!rotein that is e;!ressed in melanocytes)"

• A second gene for green has also been !ostulated"

• Ither eye colors including grey and hael are not yet

e;!lained"


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-ye Color ' %$o Genes Model

• 1or gene 2 (bey)# there are t$o !ossibilities#bro$n or blue" %he bro$n is over the blue one"

• • 1or gene , (gey)# there are t$o !ossibilities#

green or blue" Green is blue and so Gusually re!resents green and b# blue"

"• 5ro$n is dominant over greenLif you have a 5version of gene 2 and a G version of gene ,# you$ill have bro$n eyes"


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-!idermylosis bullosa

• A genetic disease that affects 2&23#333 children

• 7ac* of collagen ty!e ?? that anchors s*in andlining of gastrointestinal system to the body

• %he s*in is fragile# tearing and blistering occur$ith minimal friction

• Solid food !roduces erosions of the eso!ahgus

• Circulation stem cells from umbilical cord $ereused for treatment


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Metabolic Disorders

Disorders of carbohydrate metabolism#amino acid metabolism# organic acid

metabolism# or lysosomal storagediseases


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Al*a!tonuria

• Al*a!tonuria (blac* urine disease)' s$eat# urineof bro$n color ' a rare inherited genetic disorder of

" %his is an autosomal

recessive condition that is due to a defect in theenyme homogentisate 2#,dio;ygenase $hich!artici!ates in the degradation of tyrosine"

• A to;ic tyrosine by!roduct called homogentisicacid (or al*a!ton) accumulates in the blood# and

is e;creted in urine in large amounts" -;cessivehomogentisic acid causes damage to cartilage(leading to osteoarthritis) and heart valves as$ell as !reci!itating as *idney stones"


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+henyl*etonuria (+N=)

• Ine of the first disorders for $hichbiochemical basis $as revealed

• +henyl*etonuria (+N=) is a genetic disorder

in $hich the body canOt !rocess amino acid!henylalanine (+he) ' essential aa"


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+henyl*etonuria (+N=)

• Iccurs in about 2 in 2,#333 Caucasian births

• Caused by a recessive mutation of a gene onchromosome 2, (an autosome) at !osition

2,q,.• Gene codes for an enyme !henylalaninehydro;ylase# $hich converts +he into tyrosine

• %yrosine is needed for !rotein synthesis#

!roduction of hormones thyro;ine andandrenaline# !roduction of melanin

• Has effect


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7ysosome Storage Diseases

• iemann+ic* syndrome

' Affects brea*do$n and use of fats andcholosterol

' Causes harmful amount of li!ids to acumulatein the s!leen# liver# lungs# bone marro$

' +atients die before 23 years old

' /33 *no$n cases $orld$ide


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lin*ed ?nheritance

lin*ed dominant

lin*ed recessive


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lin*ed Dominant ?nheritance

-;am!le& vitamin D resistant ric*ets ' insufficient indigestion of vitamin D#

bone deformities


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lin*ed recessive %raits

Hemo!hilia# color blindness


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Change ?n %he Chromosomal

umber Autosomal or se; chromosomes


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Do$n Syndrome

• chromosome ' chr,2 andEor translocation of chr2.

• Similar !henoty!e

• Mental retardation

• Absence of tumors


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%urner Syndrome

• Affected individuals $ith %urnerOssyndrome (%S) are genetically ./#

• %S females have several distinguishing

characteristics such as short stature# $ebbed s*in behind the

nec*# lo$ hairline# $idely s!aced ni!!les#small breast develo!ment# bro$n s!ots#small finger nails# and ovarian failure


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Nleinfelter ofcases# and maternal nondisKunction in meiosis ?

accounts for >. of cases"• distinguishing characteristics such as

# tall stature# long arms and legs#lan*y build# feminied !hysique# lo$ testosteron levels


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?m!rinting

• %he e;!ression of some traits may de!end u!on $hich !arentcontributes the alleles for those traits"

• %$o genetic disorders# Prader-Willi syndrome and Angelmansyndrome# are caused by the same deletion on chromosome 2/"%he sym!toms differ de!ending u!on $hether the gene $asinherited from the mother or from the father"

• • Prader-+illi syndrome is caused by a deletion from the paternal version of chromosome 2/" %he syndrome is characteried bymental retardation# obesity# short stature# and unusually small handsand feet" (18IM %H- 1A%H-8)

• • ,ngelman syndrome is caused by a deletion from the maternal version of chromosome 2/" %his syndrome is characteried byuncontrollable s!ontaneous laughter# Ker*y movements# and othermotor and mental sym!toms" (18IM %H- MI%H-8)

% t il bl t d t i i t if


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• %ests are available to determine in utero if achild has a !articular disorder"

• Ine technique# amniocentesis# can beused beginning at the 2.th to 29th $ee* of!regnancy to assess the !resence of as!ecific disease"

' 1etal cells e;tracted from amniotic fluid arecultured and *aryoty!ed to identify somedisorders"

' Ither disorders can be identified from

chemicals in the amniotic fluids"


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• A second technique# chorionic vill"ssampling (C) can allo$ faster

*aryoty!ing and can be !erformed as earlyas the eighth to tenth $ee* of !regnancy" ' %his technique e;tracts a sam!le of fetal tissue

from the chrionic villi of the !lacenta"

' %his technique is not suitable for tests requiringamniotic fluid"


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Ha!loty!e

• %he DA sequence of any t$o !eo!le is 00"0 !ercent identical" %hevariations# ho$ever# may greatly affect an individualOs disease ris*"

• Sites in the DA sequence $here individuals differ at a single DAbase are called single nucleotide !olymor!hisms (S+s)"

• Sets of nearby S+s on the same chromosome are inherited in

bloc*s"• %his !attern of S+s on a bloc* is a ha!loty!e"• 5loc*s may contain a large number of S+s# but a fe$ S+s are

enough to uniquely identify the ha!loty!es in a bloc*"

• %he Ha!Ma! is a ma! of these ha!loty!e bloc*s and the s!ecificS+s that identify the ha!loty!es are called tag S+s"

htt!&EE$$$"genome"govE!age"cfmP!age?D6233329BB


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Getting =! Close and

+ersonal ith :our Genome A ne$ ty!e of com!any is offering

to scan a !erson


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Genome Analysis

• 7ast month# the =nited States Senateunanimously !assed a measure e;!ectedto encourage Americans to ta*e

advantage of genetic testing"• hen signed into la$# the Genetic

?nformation ondiscrimination Act (G?A)$ill !rotect individuals against healthinsurance and em!loyment discriminationbased on their genetic information"


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S+s

• ,>andMe and other similar com!aniesLincluding deCID-Me (an offshoot of deCID-+harmaceuticals in ?celand# founded bygeneticist Nari Stefansson) and Californiabased

avigenicsLdetermine the !attern of hundredsof thousands of singlenucleotide!olymor!hisms (S+s) across a !erson


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Genome Scans

• 1or ,"/ ml of saliva and =SQ000# ,>andMe# agenetics startu! com!any $ith headquarters inCalifornia# delivers genetic information on 93 orso conditionsLfrom ty!e ?? diabetes to ear$a;ty!e"

• :ou can also find out about your maternal and!aternal ancestry and $hether they sharecommon ancestors $ith 5en 1ran*lin or =,Rsfrontman 5ono"

• ?t analyes about 933# 333 S+s

BIOL 3301 - Genetics Ch2C - Human Genetics St

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Transcript of BIOL 3301 - Genetics Ch2C - Human Genetics St