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Non
-Men
delia
nin
herit
ance
Focu
s on
Hum
an D
isor
ders
Pete
r K. R
ogan
, Ph.
D.
Labo
rato
ry o
f Hum
an M
olec
ular
Gen
etic
sC
hild
ren’
s M
ercy
Hos
pita
lSc
hool
s of
Med
icin
e &
Com
pute
r Sci
ence
and
Eng
inee
ring
Uni
vers
ity o
f Mis
sour
i-Ka
nsas
City
http
://w
ww
.sce
.um
kc.e
du/~
roga
np
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Cau
ses o
f Non
-Men
delia
nph
enot
ypes
•Sp
orad
ic m
utat
ions
•
Ger
mlin
em
osai
cism
•R
educ
ed p
enet
ranc
e•
Var
iabl
e ex
pres
sivi
ty•
Plei
otro
py•
Locu
s Het
erog
enei
ty
Sing
le g
ene
effe
cts
•M
ulti-
hit a
nd a
cqui
red
mut
atio
ns•
Gen
omic
impr
intin
g •
Mito
chon
dria
ltra
nsm
issi
on•
Ant
icip
atio
n
Com
plex
inhe
rita
nce
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Spor
adic
mut
atio
ns•C
hrom
osom
al: n
on-d
isju
nctio
n, a
neup
loid
yof
ten
mat
erna
lly d
eriv
ed, m
ost c
omm
on (~
50%
of a
ll co
ncep
tions
)•O
ther
mut
atio
ns:
•the
mos
t fre
quen
t de
novo
intr
agen
icde
letio
nsoc
cur
in la
rge
or d
uplic
ated
gen
es (e
g.
Dys
trop
hin,
neu
rofib
rom
in, 2
1-hy
drox
ylas
e).
•poi
ntm
utat
ions
-ofte
n pa
tern
ally
der
ived
, m
ost a
re p
riva
te, b
ut h
ot sp
ots h
ave
been
not
ed
(FG
FR1)
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Ger
mlin
em
osai
cism
:mec
hani
sm
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Ger
mlin
eM
osai
cism
:exa
mpl
e
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Pene
tranc
e
Def
initi
on: R
efer
s to
all-o
r-no
n ex
pres
sion
of a
mut
ant
geno
type
. Usu
ally
a d
omin
ant t
rait
in h
eter
ozyg
ote.
If c
ondi
tion
expr
esed
in <
100%
of t
hose
with
mut
atio
n, sa
id to
hav
e re
duce
d pe
netr
ance
.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Age
-rel
ated
pen
etra
nce
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Var
iabl
e ex
pres
sivi
ty
Def
initi
on: T
he e
xten
t to
whi
ch a
gen
etic
def
ect i
s exp
ress
ed.
If th
ere
is v
aria
ble
expr
essi
vity
, the
trai
t may
var
y in
exp
ress
ion
from
mild
to se
vere
, but
it is
nev
er c
ompl
etel
y un
expr
esse
d in
in
divi
dual
s with
the
corr
espo
ndin
g m
utan
t gen
otyp
e.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Plei
otro
py
Def
initi
on: M
ultip
le p
heno
typi
c ef
fect
s of a
sing
le g
ene
or p
air o
f al
lele
s. Th
e te
rm is
use
d pa
rticu
larly
whe
n th
e ef
fect
s are
thou
ght
to b
e un
rela
ted.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Exam
ple:
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Locu
s het
erog
enei
tyD
efin
ition
: The
situ
atio
n in
whi
ch m
utat
ions
at 2
or m
ore
dist
inct
gene
loci
can
pro
duce
the
sam
e or
clo
sely
sim
ilar p
heno
type
s.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Pred
ispo
sitio
nto
can
cer:
germ
line
mut
atio
ns in
tu
mor
supp
ress
or
gene
s
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
The
neop
last
icph
enot
ype
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Exam
ples
:si
s,er
bA,sr
c,ra
f1
H-r
as,a
bl,tr
k
jun
myb
,fos,m
yc
Gro
wth
fact
orR
ecep
tor
Prot
ein
kina
se,
G-p
rote
inTr
ansc
riptio
n fa
ctor
Nuc
lear
DN
Abi
ndin
g pr
otei
ns
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Gen
omic
impr
intin
gD
efin
ition
: a p
roce
ss in
whi
ch g
enet
ic m
ater
ial i
s exp
ress
ed
diff
eren
tly w
hen
inhe
rited
from
the
mot
her t
han
whe
n in
herit
ed
from
the
fath
er.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Mito
chon
dria
linh
erita
nce
Def
initi
on: I
nher
itanc
e of
a d
isor
der e
ncod
ed b
y th
e m
itoch
ondr
ial
geno
me.
Alw
ays m
ater
nal;
hund
reds
to th
ousa
nds o
f mtD
NA
geno
mes
per
cel
l. B
ecau
se o
f het
erop
lasm
y*, o
nly
thos
e pr
ogen
yw
ith m
utan
t mtD
NA
exce
edin
g a
thre
shol
d w
illex
hibi
t an
abno
rmal
phe
noty
pe.
*Het
erop
lasm
y: T
he e
xist
ence
of d
iffer
ing
DN
A se
quen
ces a
t a lo
cus
with
in a
sing
le c
ell.
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Mito
chon
dria
linh
erita
nce:
ped
igre
e
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Phen
otyp
es o
f mito
chon
dria
ldi
sord
ers
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Gen
etic
ant
icip
atio
nD
efin
ition
: Ter
m u
sed
to d
enot
e pr
ogre
ssiv
ely
earli
er a
ppea
ranc
e an
d in
crea
sed
seve
rity
of a
dis
orde
r in
succ
essi
ve g
ener
atio
ns.
Unt
il its
mol
ecul
ar b
asis
was
und
erst
ood,
it w
as th
ough
t to
resu
ltfr
om b
iase
d as
certa
inm
ent.
Exam
ple
diso
rder
s inc
lude
:Fr
agile
X d
isea
seM
yoto
nic
dyst
roph
ySp
inoc
ereb
ella
rata
xia
Hun
tingt
on d
isea
seX
-link
ed sp
inal
bul
bar m
uscu
lar a
troph
yFr
eidr
ich’
sata
xia
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
A
B
C
30175
n=90
0(G
CT)
n
A
B
C
Bio
logi
cal b
asis
of a
ntic
ipat
ion
The
dise
ase
mut
atio
ns a
re e
xpan
ded
trinu
cleo
tide
repe
ats t
hat l
ie w
ithin
th
e af
fect
ed g
ene.
The
num
ber o
f re
peat
s inc
reas
es in
eac
h su
cces
sive
gene
ratio
n. E
xpan
sion
of t
heD
NA
repe
ats (
prob
ably
by
slip
ped
mis
pairi
ng) h
as b
een
show
n to
cau
sean
ticip
atio
n in
Fra
gile
X sy
ndro
me,
myo
toni
cdy
stro
phy,
spin
ocer
ebel
lar
atax
ia (b
ut n
ot in
spin
al b
ulba
r m
uscu
lar a
troph
y).
Pete
r K. R
ogan
, Ph.
D.
Non
-Men
delia
n in
herit
ance
Sum
mar
y: N
on-M
ende
lian
inhe
ritan
ce
•In
com
plet
e pe
netra
nce
and
varia
ble
expr
essi
vity
prod
uce
devi
atio
ns fr
om e
xpec
ted
inhe
ritan
ce p
atte
rns f
or
Men
delia
ndi
seas
es.
•C
erta
in ty
pes o
f spo
radi
cm
utat
ions
may
be
quite
com
mon
-no
fam
ily h
isto
ry is
evi
dent
.•
Pare
nt o
f orig
inef
fect
s, m
itoch
ondr
iald
isea
se, g
erm
line
inst
abili
tyor
mul
ti-hi
tmut
atio
n m
echa
nism
s als
o al
ter
inhe
ritan
ce p
atte
rns.
How
ever
, the
gen
etic
lesi
on m
ust b
e kn
own
to p
redi
ct w
ho is
at r
isk.
