4/1/2014

What

is human genetics?

The

Central Dogma of molecular biology and

genetics

DNA

to the chromosome

Mutation
Genetics

(base level & chromosome level)

and inheritance

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4/1/2014

Human genetics is the study of the human genes

Study of the genes and they role in: Cells organism

population

Genes is DNA segments that have a functional role in the

cell and are responsible for inheritance of traits (gametes)
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DNA carries the genetic information of a cell and consists of

thousands of genes which serves as a recipe on how to build a
protein molecule Proteins perform important tasks for the
cell functions it could be autocrine, paracrine, endocrine
system.
Glossary: DNA replication; transcription; translation

Human genetics, Faculty of Medicine

Brawijaya University

Gene activity can be

turned on and off at the
level of transcription by
protein factors interaction
with promoter that can
prevent or allow
transcription (e.g.
transcription factor)
Protein factor present in a
certain type of cells
Human pancreatic cells
insulin
Progenitor RBC
hemoglobin

Although, progenitor RBC

embryo embryonic
hemoglobin
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Keywords:
Zygote
differentiated cells
human

Gamete cells, meiosis

Somatic cells, mitosis

Haploid (n, 23
chromosomes)
Diploid (2n, 46
chromosomes)
Note:
Undifferentiated cells
pluripotent stem
cells

Human genetics, Faculty of Medicine

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Sister chromatid

Spacer DNA plus

H1 histone

Oktamer histone

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Cytogenetics: the study

of chromosome and cell
division

Chromosome can be seen

clearly during
metaphase, maximally
condensed

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Chromosome banding staining (Giemsa) for identification and

detection if any abnormality >4Mbp

The light bands on chromosome regions rich in GC and genes.

Dark bands rich in AT and few on genes. Ex: Chromosome 19, dense
with genes, has few dark bands.

Metaphase
spread
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Idiogram

46,XY

Fig. normal male karyotyping

Human genetics, Faculty of Medicine

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p/short
arm

q/long
arm

Telocentric

Absence in human

Some authors denotes extreme

acrocentric chr in human as telocentric,
such as: 21, 22, Y

Acrocentric: 13, 14, 15, 21, 22

Submetacentric
Metacentric

Chromatid; double =
sister chromatid
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Is a change in the genetic material

Can occur in non-coding or coding sequences

Mutation in promoter regions harmful

Somatic cells is not transmitted to offspring ( germinal
cells)

Can occur in base level and chromosome level

Base level mutation, example:

Wild type: (DNA) AAA CUC CAC UUC UUC

(protein) phe glu val lys lys
Mutant
AAA CUC C ACU UCU UC (deletion
frameshift)
phe glu (stop) xxx xx premature termination
truncated protein
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Class

Group

Stable/
fixed

Synonymous Substitution

Type

NonSubstitution
synonymous - Missense
- Nonsense
Deletion/
insertion
Dynamic
/
unstable

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Triple repeat Expansion

Effect on protein product

Silent mutation/same aa no effect

Diff aa:
Chemically diff chemically similar
(no effect)
Stop codonloss of
function/activity/stability
Frameshift/premature termination
Altered gene expression/transcription
The repeat will be increase in next
generation, ex: fragile X, Huntington
disease, myotonic dystrophy

Human genetics, Faculty of Medicine

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4/1/2014

Abnormalities of chromosome:
1.
Numerical (~heteroploid):
Polyploidy: addition one or more complete haploid
chr. (n)

Triploidy (3n); tetraploidy (4n)

Aneuploidy: loss or gain of one or more chromosomes,

the most common mechanism is in meiotic
nondisjunction (during M1/M2, usually during M1)
Monosomy (lethal in autosomal chr.), exception monosomy X
chromosome (Turner syndrome, 45,x); Trisomy:
Trisomy:
Autosomal chr.: trisomy 13, trisomy 18, trisomy 21.
Sex chr.: klinefelter syndrome (47,xxy), xyy syndrome
(47,xyy), trisomy X (47,xxx)

2.17

Structural

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Nondisjunction is failure
of homologous chr or
sister chromatids to
separate during
formation of daughter
cells.
ND could happened
during meiosis or
mitosis.
Mitotic nondisjunction
gives consequences
mosaicism
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Occur during mitosis after conception

Earlier more severe

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If parent(s) has:

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Somatic mosaicism not inherited

Gonadal/germline mosaicism could be inherited

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The most common chromosomal aneuploidy

An extra genetic material from chromosome 21 results
from:
~95%: Nondisjunction of chromosome 21 during meiosis
(classic trisomy/nonfamilial; recurrence risk is <1%)
because of maternal (~95%) and paternal (~5%) origin due
to:

1.

Aging of ova in meiosis I

Delayed fertilization cause aging of ova in meiosis II
Aging of sperm

2. ~4%: Unbalanced translocation

3. ~1%: mosaicism , the person who has 2 cell lines, 1 normal
and 1 with trisomy 21 due to mitotic nondisjunction.
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45,X
Turner syndrome

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Triploidy (3n)
Miscarriage tissue
remnant

69,XXY

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Translocations

1.

Deletion
Insertion
Invertion

2.
3.
4.

5.
6.

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Reciprocal
Robertsonian

Pericentric
Paracentric

Ring chromosome
Isochromosome
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Reciprocal:

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involves breakage of at
least 2 chromosomes
with exchange of the
fragments; common in
chr. 11 and 22
Chromosomes
involved in the
translocations cannot
pair normally with
their homolog to form
bivalent during M1
(profase) then form a
cluster called pachytene
quadrivalent
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Robertsonian

Results from breakage of

two acrocentric
chromosomes
(13,14,15,21,22) at or close
to their centromeres with
subsequent fusion of
their long arms (the short
arms/satellite of each
chromosome are lost).
Total chromosomes
number is reduced to 45.
Common in
chromosomes 13 and 14.

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Deletions

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The loss of part of a

chromosome and results in
monosomy for that segment
of the chromosomes.

Insertions

A segment of one
chromosome becomes
inserted into another
chromosome.

Duplication

Ring chromosome

Isochromosome
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Human genetics, Faculty of Medicine

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True of false:
1. Normally, a person has 46 chr in his/her karyotype.
2. Nondisjunction can occur during meiosis I or II.
3. During MI chromatids separate and during MII the
members of homologous pair separate.
4. Half of your chr were inherited from your father and
half were inherited from your mother.
5. Somatic mutation will transmit to the offspring.
Fill the blanks:
1. If the parental cell has 24 chr, the daughter cells
following meiosis will have.chr.
2. Post-fertilization mutation will result.
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Human genetics, Faculty of Medicine

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True of false:
1. Normally, a person has 46 chr in his/her karyotype. (T)
2. Nondisjunction can occur during meiosis I or II. (T)
3. During MI chromatids separate and during MII the
members of homologous pair separate. (F)
4. Half of your chr were inherited from your father and
half were inherited from your mother. (T)
5. Somatic mutation will transmit to the offspring. (F)
Fill the blanks:
1. If the parental cell has 24 chr, the daughter cells
following meiosis will have.chr. (12)
2. Post-fertilization mutation will result. (mosaicism)
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Classical patterns:

Dominant

Recessive

Autosome

Autosomal dominant:
- males ~ females
- both sexes could be
affected
- could be found in every
generation
- male to male transmission

Autosomal recessive:
-Males ~ females
- both parents are carriers
- Increased incidence of
parental consanguinity

Sex
chromosome
(e.g. chr X)

X-linked dominant:
- ~ X-linked recessive due to
X inactivation (mutant allele
is expressed in only a
proportion of cells)

X-linked recessive:
-Males affected almost
exclusively
- transmission through carrier
female
- no male to male transmission
- all daughters of affected
males are carriers

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Dominant
Recessive

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One traits is governed by

two or more sets of alleles,
possibly located on many
different pairs of chr.
The more genes involved
more variation
phenotypes.
Skin color; body heights

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Human genetics, Faculty of Medicine

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When the traits is

controlled by multiple
allele.
Blood types is
controlled by 3 alleles
(A, B, none/O)
Codominant

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Human genetics, Faculty of Medicine

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1.

What is the darkest child that could result from a

mating between light and very light individual?

2.

What is the lightest child that could result from a

mating between two medium-brown individuals?

3.

Determine which baby belongs to which parents:

baby 1, type O; baby 2, type B
Mrs Ahmad, type A; Mr Ahmad, type A
Mrs Doni, type A; Mr Doni, type AB

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Human genetics, Faculty of Medicine

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What is the darkest child that could result from a

mating between light and very light individual?
Light

What is the lightest child that could result from a

mating between two medium-brown individuals?
Very light

Determine which baby belongs to which parents:

baby 1, type O; baby 2, type B
Mrs Ahmad, type A; Mr Ahmad, type A
Mrs Doni, type A; Mr Doni, type AB
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Human genetics, Faculty of Medicine

Brawijaya University

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Human genetics, Faculty of Medicine

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Documentation of family
history.
Record:

I
II
III

names, DOB, appropriate

medical record, age of onset
of disease, symptoms.

Specific questions related

to genetic diseases:

miscarriage, stillbirth, infant

death, consanguinity.

IV
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Human genetics, Faculty of Medicine

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1.

A woman is color blind. What are the chances that

her sons will be color blind? If she is married to a
man with normal vision, what are the chances that
her daughters will be color blind? Will be carriers?

2.

Both the husband and wife have normal vision.

The wife gives birth to a color-blind daughter.
What can you deduce about the girls parentage?

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Human genetics, Faculty of Medicine

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1.

A woman is color blind. What are the chances that

her sons will be color blind? If she is married to a
man with normal vision, what are the chances that
her daughters will be color blind? Will be carriers?
Answer: 100%; none; 100%

2.

Both the husband and wife have normal vision.

The wife gives birth to a color-blind daughter.
What can you deduce about the girls parentage?
Answer: The husband is not the father.

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Human genetics, Faculty of Medicine

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Kingston HM., 2002. ABC Clinical Genetics. BMJ

Books, London.
Sadler TW., 2009. Langmans Medical Embryology 9th
ed.

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