1

1M

CB

140

12-

4-06

Nos

ce te

ipsu

m:

the

hum

an g

enom

eP

art I

I: ge

netic

s, d

iagn

ostic

s, a

nd

gene

ther

apy

of in

herit

ed d

isea

se

2M

CB

140

12-

4-06

Impo

rtant

dis

tinct

ion

1.“M

onog

enic

dis

orde

rs” –

hum

an d

isea

ses

who

se

etio

logy

can

in s

ome

mor

e or

less

line

ar fa

shio

n be

tra

ced

to a

sin

gle-

locu

s ge

netic

lesi

on.

2.D

isea

ses

with

a “g

enet

ic

com

pone

nt” o

r a “g

enet

ic

pred

ispo

sitio

n” –

diso

rder

s th

at m

anki

nd is

kno

wn

to b

e ge

netic

ally

pol

ymor

phic

for

(in te

rms

of s

usce

ptib

ility

) at

mul

tiple

loci

.3.

All

othe

r dis

ease

(tha

t may

or

may

not

be

trans

crip

tion

base

d).

1.P

heno

men

a af

fect

ing

ploi

dy (e

.g.,

aneu

ploi

dies

suc

h as

D

own,

Edw

ards

, Tur

ner,

Klin

efel

ter)

.2.

Phe

nom

ena

affe

ctin

g ch

rom

osom

e st

ruct

ure

(e.g

., tra

nslo

catio

ns in

le

ukem

ia).

3.P

heno

men

a af

fect

ing

sing

le lo

ci (g

enes

or

rela

tivel

y sm

all

chro

mos

omal

se

gmen

ts).

3M

CB

140

12-

4-06

Arc

hiba

ld G

arro

d (1

902)

Hig

her f

requ

ency

of c

hild

ren

with

alk

apto

nuria

(urin

e tu

rns

dark

on

stan

ding

and

alk

alin

izat

ion)

from

con

sang

uine

ous

mar

riage

s.W

hy?

“The

re is

no

reas

on to

sup

pose

that

mer

e co

nsan

guin

ity o

f pa

rent

s ca

n or

igin

ate

such

a c

ondi

tion

as a

lkap

tonu

ria in

th

eir o

ffspr

ing,

and

we

mus

t rat

her s

eek

an e

xpla

natio

n in

so

me

pecu

liarit

y of

the

pare

nts,

whi

ch m

ay re

mai

n la

tent

fo

r gen

erat

ions

… It

has

rece

ntly

bee

n po

inte

d ou

t by

Bat

eson

that

the

law

of h

ered

ity d

isco

vere

d by

Men

del

offe

rs a

reas

onab

le a

ccou

nt o

f suc

h ph

enom

ena.

…””

http

://w

ww

.esp

.org

/foun

datio

ns/g

enet

ics/

clas

sica

l/ag-

02.p

df

Gar

rod

(190

2) L

ance

t 2: 1

16.

4M

CB

140

12-

4-06

Gar

rod

(190

2) L

ance

t 2: 1

16.

2

5M

CB

140

12-

4-06

Sic

kle-

cell

anem

ia –

a br

ief h

isto

ry“In

the

wes

tern

lite

ratu

re, t

he fi

rst

desc

riptio

n of

sic

kle

cell

dise

ase

was

by

a C

hica

go p

hysi

cian

, Ja

mes

B. H

erric

k, w

ho n

oted

in

1910

that

a p

atie

nt o

f his

from

th

e W

est I

ndie

s ha

d an

ane

mia

ch

arac

teriz

ed b

y un

usua

l red

ce

lls th

at w

ere

sick

le-s

hape

d.”

By

1923

, it w

as re

aliz

ed th

e co

nditi

on is

her

edita

ry.

In 1

949,

Nee

l rea

lized

that

pa

tient

s w

ith S

CA

are

ho

moz

ygou

s, a

nd h

eter

ozyg

ous

carri

ers

have

a m

uch

mild

er

cond

ition

(sic

kle

cell

trait)

.

6M

CB

140

12-

4-06

Sic

kle

cell

anem

iaN

IH:

“Sic

kle

cell

anem

ia is

the

mos

t co

mm

on in

herit

ed b

lood

di

sord

er in

the

Uni

ted

Sta

tes,

af

fect

ing

abou

t 72,

000

Am

eric

ans

or 1

in 5

00 A

frica

n A

mer

ican

s. S

CA

is

char

acte

rized

by

epis

odes

of

pain

, chr

onic

hem

olyt

ic a

nem

ia

and

seve

re in

fect

ions

, usu

ally

be

ginn

ing

in e

arly

chi

ldho

od.”

7M

CB

140

12-

4-06

Linu

s P

aulin

g, 1

949:

HbS

has

diff

eren

t cha

rge!

!

8M

CB

140

12-

4-06

V. I

ngra

m, N

atur

e 19

56“O

n [th

e ex

istin

g] e

vide

nce

alon

e, it

is n

ot p

ossi

ble

to

deci

de w

heth

er th

e di

ffere

nce

betw

een

the

prot

eins

, w

hich

is in

any

eve

nt s

mal

l, lie

s in

the

amin

o-ac

id

sequ

ence

s of

the

poly

pept

ide

chai

ns, o

r whe

ther

it li

es

in th

e fo

ldin

g of

thes

e ch

ains

lead

ing

to th

e m

aski

ng o

f so

me

amin

o-ac

id s

ide

chai

ns.”

Exp

erim

ent:

1.D

iges

t Hb

A a

nd H

b S

with

tryp

sin

(pro

teas

e –

cuts

he

mog

lobi

n in

to ~

30 p

eptid

es).

2.S

epar

ate

resu

lting

frag

men

ts b

y el

ectro

phor

esis

, and

th

en b

y ch

rom

atog

raph

y.3.

Trac

e th

e pe

ptid

e m

ap.

V. I

ngra

m (1

956)

Nat

ure

178:

792

.

3

9M

CB

140

12-

4-06

V. I

ngra

m (1

956)

Nat

ure

178:

792

.10

MC

B 1

40 1

2-4-

06

“One

can

now

ans

wer

at l

east

par

tly th

e qu

estio

n pu

t ear

lier,

and

say

ther

e th

ere

is a

di

ffere

nce

in th

e am

ino-

acid

seq

uenc

e in

on

e sm

all p

art o

f one

of t

he p

olyp

eptid

e ch

ains

. Thi

s is

par

ticul

arly

inte

rest

ing

in v

iew

of

the

gene

tic e

vide

nce

that

the

form

atio

n of

hem

oglo

bin

S is

due

to a

mut

atio

n in

a

sing

le g

ene.

”

V. I

ngra

m (1

956)

Nat

ure

178:

792

.

11M

CB

140

12-

4-06

11.7

12M

CB

140

12-

4-06

SC

A1.

Fairl

y ho

mog

eneo

us g

enet

ic b

asis

–an

A-to

-T

trans

vers

ion

in th

e si

xth

codo

n of

the

HB

B g

ene

that

le

ads

to a

glu

→va

l sub

stitu

tion

(→R

FLP

!)2.

In N

orth

Am

eric

a, h

eter

ozyg

osity

for m

utan

t alle

le is

la

rgel

y as

ympt

omat

ic (s

ickl

e ce

ll tra

it), b

ecau

se

conc

entra

tion

of h

emog

lobi

n S

is n

ot h

igh

enou

gh fo

r th

e er

ythr

ocyt

es to

sic

kle.

3.In

are

as w

ith h

igh

inci

denc

e of

mal

aria

, the

fitn

ess

of

hete

rozy

gote

s is

gre

ater

than

of n

onca

rrie

rs o

r affe

cted

in

divi

dual

s (o

verd

omin

ance

) bec

ause

car

riers

are

re

lativ

ely

mal

aria

-res

ista

nt, e

xpla

inin

g th

e hi

gh

frequ

ency

of t

his

alle

le.

4.Th

erap

y –

hydr

oxyu

rea

(wak

es u

p em

bryo

nic

and

feta

l gl

obin

gen

es),

mor

phin

e fo

r the

pai

n, a

nd p

roph

ylac

tic

peni

cilli

n. “S

ickl

e ce

ll an

aem

ia. A

sim

ple

dise

ase

with

no

cur

e” (N

atur

e 19

89).

4

13M

CB

140

12-

4-06

“Fun

ctio

nal c

loni

ng”

In th

e ca

se o

f alk

apto

nuria

, sic

kle

cell

anem

ia, a

nd b

lood

clo

tting

dis

orde

rs s

uch

as h

emop

hilia

, th

e di

seas

e ge

nes

is

iden

tifie

d ba

sed

on s

ome

bioc

hem

ical

or

othe

r def

ect e

xhib

ited

by th

e pa

tient

.W

hat i

f the

def

ect c

anno

t be

trace

d in

a

sim

ple

way

to a

bio

chem

ical

ph

enom

enon

?

14M

CB

140

12-

4-06

Cys

tic fi

bros

is

•M

ost c

omm

on m

onog

enic

aut

osom

al

hum

an g

enet

ic d

isor

der –

1 in

eve

ry 2

000

live

birth

s.•

q2=0

.05%

; q=2

.2%

; p=9

7.8%

; 2pq

=4%

car

riers

.•

Com

plex

dys

func

tion

of th

e lu

ngs

and

the

panc

reas

.

15M

CB

140

12-

4-06

Life

exp

ecta

ncy

of C

F pa

tient

s

16M

CB

140

12-

4-06

Map

ping

by

linka

ge(“

posi

tiona

l clo

ning

”)If

a gi

ven

mar

ker i

s lin

ked

(=is

on

the

sam

e ch

rom

osom

e as

) to

the

gene

mut

atio

ns in

w

hich

cau

se a

cer

tain

dis

ease

, the

n on

e sh

ould

be

able

to o

bser

ve c

oinh

erita

nce

of

som

e al

lelic

form

of t

hat m

arke

r to

the

occu

rrenc

e of

the

dise

ase.

“Coi

nher

itanc

e” =

occ

urre

nce

in g

enot

ype

of

two

loci

with

a fr

eque

ncy

high

er th

an

Men

del’s

sec

ond

law

allo

ws.

5

17M

CB

140

12-

4-06

11.1

718

MC

B 1

40 1

2-4-

06

Men

del’s

sec

ond

law

19M

CB

140

12-

4-06

4.17

20M

CB

140

12-

4-06

6

21M

CB

140

12-

4-06

Ver

y si

mpl

e an

d as

toni

shin

gly

influ

entia

l con

sequ

ence

of a

ll th

is s

tuff

Two

mar

kers

loca

ted

on d

iffer

ent

chro

mos

omes

will

segr

egat

e aw

ay fr

om

each

oth

er in

one

out

of t

wo

mei

oses

.

Two

mar

kers

that

are

on

the

sam

e ch

rom

osom

e w

ill te

nd to

sta

y to

geth

er.

22M

CB

140

12-

4-06

Fig.

1 N

olan

Nol

an e

t al.

Nat

. Gen

et. (

2000

). 25

: 440

.

a, N

anom

ouse

(Nan

o),

GE

NA

50. b

, Dom

inan

t sp

ottin

g (K

itW-3

9H),

GE

NA

133.

c, A

m

icro

phth

alm

ia m

utan

t, G

EN

A16

3. d

,e, B

atfa

ce, a

cr

anio

faci

al m

utan

t, G

EN

A12

3.

23M

CB

140

12-

4-06

Will

iam

Ern

est C

astle

–fo

unde

r of

mou

se g

enet

ics

1.In

bree

ding

as

a to

ol fo

r mak

ing

gene

tical

ly

unifo

rm s

train

s of

mic

e th

at a

re h

omoz

ygou

s fo

r ev

ery

alle

le in

the

geno

me.

2.B

roth

er-s

iste

r mat

ings

–m

akes

12.

5% o

f all

loci

in

the

geno

me

hom

ozyg

ous

(Cla

renc

e Li

ttle)

.

Afte

r 40

gene

ratio

ns o

f bro

ther

-sis

ter m

atin

g,

>99.

98%

of g

enom

e is

hom

ozyg

ous.

By

F 60,

mic

e ar

e co

nsid

ered

gen

etic

ally

iden

tical

to o

ne a

noth

er.

24M

CB

140

12-

4-06

11.1

2

7

25M

CB

140

12-

4-06

A B

C D

A B

C D

E F

G H

E F

G H

I J

K

L

I J

K

L

1

2

3

♂ ♀

26M

CB

140

12-

4-06

A B

C D

A B

C D

E F

G H

E F

G H

I J

K

L

I J

K

L

1

2

3

♂ ♀

x

27M

CB

140

12-

4-06

A B

C D

A B

C D

E F

G H

E F

G H

I J

K

L

I J

K

L

♂ ♀

x

Xa

b c

d

a b

c d

e f

g

h

e f

g

h

i j

k

l

i j

k

l

♂ ♀

28M

CB

140

12-

4-06

A B

C D

a b

c

d

E F

G H

e f

g

h

I J

K

L

i j

k

l

♂ ♀

x

Xa

b c

d

a b

c d

e f

g

h

e f

g

h

i j

k

l

k l

m n

♂ ♀

8

29M

CB

140

12-

4-06

A B

C D

a b

c

d

E F

G H

e f

g

h

I J

K

L

i j

k

l

♂ ♀

x

meiosis

Dur

ing

mei

osis

, the

re is

a 5

0% c

hanc

e th

at th

e m

utan

t gen

e w

ill s

epar

ate

from

al

l mar

kers

on

unlin

ked

chro

mos

omes

. Thi

s m

eans

that

ther

e is

an

equa

l lik

elih

ood

of fo

rmin

g a

gam

ete

“X E

” and

“X e

” –si

mila

rly, “

X J

” and

“X j.

”

On

the

othe

r han

d, th

e m

utan

t gen

e w

ill n

ot s

epar

ate

as fr

eque

ntly

from

m

arke

rs th

at li

e on

the

sam

e ch

rom

osom

e as

it d

oes.

In o

ther

wor

ds, t

he “X

B”

gam

ete

will

be

mor

e fre

quen

t tha

n th

e “X

b” g

amet

e. T

o id

entif

y,on

whi

ch

chro

mos

ome,

and

whe

re e

xact

ly, t

he m

utan

t gen

e lie

s, w

e ne

ed to

find

the

spec

ific

mar

ker t

hat t

he d

isea

se a

lway

s in

herit

s w

ith.

30M

CB

140

12-

4-06

A B

C D

a b

c

d

E F

G H

e f

g

h

I J

K

L

i j

k

l

♂ ♀

x

Xa

b c

d

a b

c d

e f

g

h

e f

g

h

i j

k

l

k l

m n

♂ ♀

31M

CB

140

12-

4-06

Fina

lly

Take

all

the

mut

ant c

hild

ren.

Gen

otyp

e th

em fo

r mar

kers

ove

r the

ent

ire

geno

me.

Find

the

“upp

erca

se m

arke

r” th

at o

ccur

s w

ith th

e hi

ghes

t fre

quen

cy (>

>>50

%) i

n th

e m

utan

t chi

ldre

n.

32M

CB

140

12-

4-06

A B

C D

a b

c

d

E F

G H

e f

g

h

I J

K

L

i j

k

l

♂ ♀

xx

9

33M

CB

140

12-

4-06

34M

CB

140

12-

4-06

5.12

35M

CB

140

12-

4-06

Pro

blem

Hum

ans

are

not D

roso

phila

or m

ouse

.

To m

ap g

enet

ic d

ista

nce,

one

nee

ds to

“set

up

cro

sses

” with

kno

wn

arra

ngem

ents

of

geno

type

s.

36M

CB

140

12-

4-06

The

Pro

blem

of P

hase

In h

uman

ped

igre

es, y

ou c

anno

t “se

t up

a cr

oss”

th

e w

ay y

ou w

ant t

o! E

ven

in a

sim

ple

cros

s:♂

AaBb

×♀

aabb

… y

ou re

ally

nee

d to

kno

w w

heth

er D

ad w

as

AB

/ab

or A

b/aB

in o

rder

to c

alcu

late

map

di

stan

ces

(you

nee

d to

tell

whi

ch c

hild

is

reco

mbi

nant

and

whi

ch o

ne is

n’t!!

!)

AB

ab

Ab

aB

OR

10

37M

CB

140

12-

4-06

11.1

838

MC

B 1

40 1

2-4-

06

Lod

scor

es a

nd m

appi

ng b

y lin

kage

Sol

utio

n: c

alcu

late

loga

rithm

of t

he o

dds

(lod)

that

the

pedi

gree

obs

erve

d is

due

to li

nkag

e.

For a

ny g

iven

trai

t (di

seas

e) a

nd a

ny g

iven

mar

ker b

eing

tra

cked

in th

e pe

digr

ee, t

he L

od s

core

is th

e lo

g 10

of th

e fo

llow

ing

ratio

:pr

obab

ility

that

this

ped

igre

e w

ould

be

obse

rved

if th

e tw

o lo

ci a

re li

nked

, and

are

sep

arat

ed b

y a

certa

in g

enet

ic

dist

ance

DIV

IDE

D b

y pr

obab

ility

this

ped

igre

e w

ould

be

obse

rved

if th

e tw

o lo

ci w

ere

unlin

ked.

Two

loci

are

link

ed if

the

lod

scor

e >

3B

y th

e w

ay –

a lo

garit

hm is

take

n so

that

we

can

add

lod

scor

es o

btai

ned

from

diff

eren

t fam

ilies

!!

39M

CB

140

12-

4-06

p. 3

92-3

9340

MC

B 1

40 1

2-4-

06

Whi

te e

t al (

1985

) Nat

ure

318:

382

.A

RFL

P li

nked

to C

F!!!

–“m

iddl

e th

ird o

f 7q,

nea

r met

”

11

41M

CB

140

12-

4-06

Find

ing

the

CF

gene

•Li

nkag

e an

alys

is p

lace

d th

e C

F ge

ne in

a

rath

er la

rge

(1.5

Mb)

frag

men

t of

chro

mos

ome

7 (n

ext t

o m

et)

•“J

umpi

ng a

nd w

alki

ng” –

Rom

men

s et

al

(Col

lins)

Sci

ence

245

: 105

9 (1

989)

.

42M

CB

140

12-

4-06

43M

CB

140

12-

4-06

CFT

R

•La

rge

gene

(250

kb)

•La

rge

prot

ein

(1,4

80 a

a)•

cAM

P-re

gula

ted

chlo

ride

chan

nel

•70

% o

f mut

atio

ns –

∆phe

508

(pro

tein

st

uck

in th

e E

R)

Bre

nnan

and

Ged

des

(200

2) C

urr.

Opi

n. In

fect

. Dis

. 15:

175

-182

.44

MC

B 1

40 1

2-4-

0611

.22

12

45M

CB

140

12-

4-06

11.2

246

MC

B 1

40 1

2-4-

06

Gen

e th

erap

y fo

r CF?

2002

:“S

ince

the

clon

ing

of th

e cy

stic

fibr

osis

gen

e (C

FTR

) in

1989

, 18

clin

ical

tria

ls h

ave

been

car

ried

…. M

ost t

rials

dem

onst

rate

d pr

oof-o

f-prin

cipl

e fo

r ge

ne tr

ansf

er to

the

airw

ay. H

owev

er, g

ene

trans

fer e

ffici

ency

… w

as lo

w, a

nd m

ost l

ikel

y in

suffi

cien

t to

achi

eve

clin

ical

ben

efit.

A m

ajor

func

tion

of th

e ai

rway

epi

thel

ium

is to

pr

even

t upt

ake

of fo

reig

n m

ater

ials

, inc

ludi

ng g

ene

trans

fer a

gent

s.”

Qua

si-s

ucce

ss –

rela

tive

of H

IV in

an

Ebo

la c

oat!

Grie

senb

ach

et a

l. (2

002)

Gen

e Th

er. 9

: 134

4.

47M

CB

140

12-

4-06

48M

CB

140

12-

4-06

The

“kno

ckou

t” m

ouse

A m

ouse

gen

otyp

ical

ly u

nifo

rm a

nd

hom

ozyg

ous

for a

n am

orph

ic (f

ull n

ull)

alle

le

of a

gen

e of

cho

ice.

13

49M

CB

140

12-

4-06

Em

bryo

nic

stem

cel

ls

50M

CB

140

12-

4-06

Ann

u. R

ev. C

ell D

ev. B

iol.

2001

. 17:

435-

462.

EM

BR

YO

-DER

IVED

STE

M C

ELLS

: Of M

ice

and

Men

A

ustin

G. S

mith

51M

CB

140

12-

4-06

52M

CB

140

12-

4-06

Pos

itive

-neg

ativ

e se

lect

ion

(Mar

io C

apec

chi,

1989

)N

on-H

R e

vent

s ar

e M

AS

SIV

ELY

mor

e fre

quen

t tha

n H

R e

vent

s.↓

Two

sequ

entia

l sel

ectio

n ev

ents

to e

limin

ate

all c

ells

that

und

erw

ent n

on-H

R o

r no

reco

mbi

natio

n at

all,

and

PR

ES

ER

VE

thos

e ce

lls th

at u

nder

wen

t HR

.

“Tar

getin

g co

nstru

ct”

14

53M

CB

140

12-

4-06

54M

CB

140

12-

4-06

55M

CB

140

12-

4-06

56M

CB

140

12-

4-06

15

57M

CB

140

12-

4-06

58M

CB

140

12-

4-06

Mou

se m

odel

?

p. 8

57: “

Ani

mal

s ho

moz

ygou

s fo

r the

CFT

R

knoc

kout

alle

le d

ispl

ay a

mut

ant

phen

otyp

e th

at is

ver

y si

mila

r to

that

ex

pres

sed

by h

uman

s su

fferin

g fro

m c

ystic

fib

rosi

s.”

I beg

you

r par

don?

59M

CB

140

12-

4-06

And

now

, the

trut

h

“The

airw

ays

of C

F m

ice

are

of o

bvio

us in

tere

st to

in

vest

igat

ors

beca

use

~95%

of t

he m

orbi

dity

and

m

orta

lity

in C

F hu

man

s is

due

to p

ulm

onar

y m

anife

stat

ions

of t

he d

isea

se. …

In th

e C

F pa

tient

, a c

onsi

sten

t fin

ding

in th

e ai

rway

s is

m

ucus

plu

ggin

g w

ith b

acte

rial i

nfec

tion.

…In

all

CF

mou

se m

odel

s ex

amin

ed, v

irtua

lly n

orm

al

lung

his

tolo

gy a

nd a

bsen

ce o

f muc

us p

lugg

ing

are

cons

iste

nt fi

ndin

gs (3

6, 3

9, 7

0, 7

8, 9

2, 1

03,

114,

119

).”

Gru

bb a

nd B

ouch

er (1

999)

Phy

s. R

ev. 7

9: 1

93-2

14.

60M

CB

140

12-

4-06

16

61M

CB

140

12-

4-06

A re

mar

kabl

e ex

ampl

e of

a

phen

otyp

e in

a k

nock

out m

ouse

A D

efec

t in

Nur

turin

g in

Mic

e La

ckin

g th

e Im

med

iate

Ear

ly G

ene fosB

Bro

wn

et a

l.C

ell,

Vol

. 86,

297

–309

, Jul

y, 1

996

62M

CB

140

12-

4-06

63M

CB

140

12-

4-06

64M

CB

140

12-

4-06

17

65M

CB

140

12-

4-06

“Car

rier s

cree

ning

for c

ystic

fibr

osis

, Gau

cher

dis

ease

, and

Ta

y-S

achs

dis

ease

in th

e A

shke

nazi

Jew

ish

popu

latio

n: th

e fir

st 1

000

case

s at

New

Yor

k U

nive

rsity

Med

ical

Cen

ter”

By

late

199

3, th

e ge

nes

for c

ystic

fibr

osis

and

Gau

cher

dis

ease

and

the

mut

atio

ns c

omm

on a

mon

g A

shke

nazi

Jew

s ha

d be

en id

entif

ied.

In

resp

onse

to th

ese

adva

nces

, het

eroz

ygot

e sc

reen

ing

for c

ystic

fibr

osis

an

d G

auch

er d

isea

se w

as a

dded

to th

e m

ore

than

20-

year

-old

Tay

-S

achs

dis

ease

scr

eeni

ng p

rogr

am a

t New

Yor

k U

nive

rsity

Med

ical

C

ente

r, N

ew Y

ork,

NY.

… P

atie

nts

and

thei

r ref

errin

g ph

ysic

ians

wer

e in

form

ed a

bout

the

new

car

rier t

ests

. At t

he ti

me

of s

cree

ning

, pat

ient

s co

uld

choo

se th

eir t

ests

(hex

osam

inid

ase

A b

y en

zym

e an

alys

is fo

r Ta

y-S

achs

dis

ease

or m

utat

ion

anal

ysis

for c

ystic

fibr

osis

and

Gau

cher

di

seas

e). …

The

maj

ority

of A

shke

nazi

Jew

ish

patie

nts

chos

e to

hav

e te

stin

g fo

r all

3 di

seas

es. I

f the

y pr

evio

usly

und

erw

ent s

cree

ning

for

Tay-

Sac

hs d

isea

se, t

hen

they

cho

se to

und

ergo

test

ing

for c

ystic

fib

rosi

s an

d G

auch

er d

isea

se. A

ll ca

rrier

cou

ples

for e

ach

of th

ese

dise

ases

wen

t on

to h

ave

pren

atal

test

ing.

All

mix

ed-m

arria

ge c

oupl

es

in w

hom

the

Jew

ish

partn

er w

as fo

und

to b

e a

carr

ier f

or G

auch

erdi

seas

e ch

ose

to h

ave

pren

atal

dia

gnos

is. O

ne fe

tus

was

iden

tifie

d as

ha

ving

cys

tic fi

bros

is. S

ince

the

prog

ram

was

initi

ated

, no

Ash

kena

zi

Jew

ish

baby

has

bee

n bo

rn w

ith a

ny o

f the

se d

isea

ses

at N

ew Y

ork

Uni

vers

ity M

edic

al C

ente

r.

Kro

nn e

t al.

(199

8) A

rch.

Inte

rn. M

ed. 1

58: 7

77.

66M

CB

140

12-

4-06

67M

CB

140

12-

4-06

68M

CB

140

12-

4-06