Weiying Jiang Department of Medical Genetics

Screening for genetic disease p.303

Screening

The identification of a person from a population with a particular disorder , or who carry a gene for a particular disorder.

Carrier testing for autosomal and recessive and X-linked disorders

Carrier ?

Carrier

Normal in appearance

An individual who is heterozygous for a recessive gene that predisposes for a hereditary disease.

An individual who has a disease –caused dominant gene that is delay or irregular dominance

Carrier

An individual who has a derive chromosome of balanced translocation, balanced inversion

Normal in appearance

Carrier

An individual that carries one gene for a particular recessive trait. A carrier does not express the trait but, when mated with another carrier, can produce offspring that do.

Irregular dominance

Form fruste and delay

Balanced translocation carrier

Balanced inversion

Clinic manifestation in carrier

Most carriers of

AR and XR are

no manifestation

overlapping variation seen in the general population

Overlapping variation seen in the general population

0

10

20

30

40

50

60

70

80

90

100

0.5 1 1.5 2

Normal

Heterozygote

Clinic manifestation in carrier

A few carriers of XR have mild clinic manifestation.

Careful examination

carrier of X-linked Ocular Albinism

carrier of hemophilia

X chromosome inactivity

图 3-12 X 连锁遗传女性携带者镶嵌体的形成

F M

合子

巴氏小体

早期胚胎

Biochemical abnormality

carriers of

AR and XR areEnzymatic activity levels in carriers overlap with those in normal range

Detectable biochemical abnormality in carriers of certain diseases

G6PD/6PGD

0

10

20

30

40

50

60

70

80

90

100

0.5 1 1.5 2

Normal

Heterozygote

Normal G6PD/6PGD:1-1.67

G6PD/6PGD Ratio

Num

bers

of

subj

ects

DMD

DMD hemizygote

Increased permeability of muscular membrane

Escape of the creatine kinase (CK) into blood

CK increasing

DMD- Heterozygote

0

10

20

30

40

50

60

70

80

1 2 3 4

Nornal

Hterozygote

CK: µMol/L

Num

bers

of

the

hete

rozy

gote

Biochemical abnormality

Tay-Sachs Disease

Carrier testing

Select life partner

Faith-based objection to

termination of pregnancy

Linkage between a disease locus and a polymorphic maker p.305

RFLP (Restriction fragment length polymorphism)

STR （ short Tandem Repeat ）

SNP （ Single Nucleotide Polymorphism ）

Mother Father

A

b

A

b

a

B

A

B

A

B

a

Ba

B

A

B

A

b

X-linked recessive inheritance

RFLP

STR （ short Tandem Repeat ）

Stands for “CA”

Ⅰ

Ⅱ

Ⅲ

1 2

1 2 3 4

1 2 3 4

Obligate carrier

DMD

SNP （ Single Nucleotide Polymorphism ）

Neonatal screening P310

AminoNova services and aminoNova analyzers

Phenylketonuria (PKU)

Classical Phenylketonuria (PKU)

Phenylalanine hydroxylase

phenylalanine tyrosine

Phenylpyruvic Acid

Phenyllactic Acid Phenylacetic Acid

Phenylpyruvic Acid Sweat

Phenyllactic Acid Urine

Phenylacetic Acid

Bad smell

(stink like mouse urine)

Phenylpyruvic Acid γ aminobutyric

Phenyllactic Acid Acid

Phenylacetic Acid serotonin(5-HT)

CNS

Mental Retardation

Phenylalanine Acid

Phenylalanine hydroxylase

tyrosine

tyrosinase (-)

dopa melanin

skin

Pigment eyes

hair

Bacillus subtilis inhibition assay is a medical test performed on newborn infants to detect phenylketonuria.

Bacillus subtilis inhibition assay (Guthrie test)

A spot of blood on a filter paper disc is placed on

the surface of an agar plate containing β-2-

thienylalanine that inhibits the growth of bacteria.

However, the inhibition can be overcome by high phe. After incubating the agar plate overnight, the diameter of the growth zone around the test disc is compared to that of a control disc of blood serum to which a known quantity of phe. has been added. This permits one to estimate the amount of phe in the test disc

Standard concentration ：

2 ， 4 ， 6 ， 8 ， 12 ， 20mg/dl

Compare with the sample

2 ， 4 ， 6 ， 8 ， 12 ， 20mg/dl

AminoNova services and aminoNova analyzers

Mass-spectrum

G6PD detecting

Population screening p311

Thalassemia

α-Thalsssemia

β-Thalsssemia

Blood cell analysis :

mean corpuscular volume (MCV) > or =80fl

mean corpuscular Hb (MCH) > or = 25

Normal

α-Thalsssemia

β-Thalsssemia

Biochemical testing:

Sickle-cell disease

Β-code 6 GAG > GTG

Glu.> Val.

Sickle hemoglobin

Polymerization

distortion

Reducing deformability