Duplications (dup) The orientation of duplications is either - PowerPoint Presentation

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Duplications (dup)

The orientation of duplications is either

direct

or

inverted

and is indicated by the order of the bands with respect to the centromere in the karyotype designation.

The band closest to the centromere is written first in the short system; only the detailed system can pinpoint the exact location of the duplicated segment.

46,XY,dup(1)(q21q42)

This is a

direct duplication

of the segment between

bands

q21 and q42 in the long arm of chromosome 1.

46,XX,dup(13)(q34q21)

This is an

inverted duplication

of the segment

between bands q21

and

q21

in the long arm of chromosome 13

.

Insertions (ins)

an insertion involves the movement of a segment of

intrachromosomal

material

from one chromosomal location into another.

The recipient can be another chromosome or a different part of the chromosome of origin.

The orientation of the inserted segment may be

direct

, retained in its original orientation, or

inverted

. In inverted insertions, the “normal” orientation of the bands will be reversed with respect to the centromere.

.

Translocations (t)

A translocation is an abnormality resulting from an

exchange of genetic material

between

two chromosomes

.

46,XY,t(12;14)(q13;q32)

This is a translocation involving two chromosomes. Breaks have occurred at bands q13 and q32.

Robertsonian

Translocations (rob)

Robertsonian

translocations are a special type of translocation in humans involving the

acrocentric chromosomes

(chromosomes 13, 14, 15, 21, and 22).

Typically, the participating chromosomes break in their short arms and give the appearance that the long arms fuse to form a single chromosome with a single centromere. If the location of the breakpoints is unproven, “rob” may be used.

Because the short arms of acrocentric chromosomes contain repetitive ribosomal gene clusters, loss of these arms due to this type of translocation has no phenotypic consequences.

A

karyotype with a single

Robertsonian

translocation by

definition

will have a 45 chromosome

count.

Derivative (der) and Recombinant (rec) Chromosomes

Derivative chromosomes are structurally abnormal chromosomes that can be generated in three ways:

More than one rearrangement within a single chromosome

One rearrangement involving two or more chromosomes including rearrangements between chromosome homologues

More than one rearrangement involving two or more chromosomes.

The term

“der”

refers to a chromosome that has an intact centromere.

Recombinant

Chromosomes

Recombinant chromosomes are structurally rearranged chromosomes with a

new segmental composition resulting from meiotic crossing-over

.

Recombinants usually originate from heterozygotes carrying inversions or insertions, and the term always refers to the chromosome that has an intact centromere.

The triplet “

rec

” should be used when

the parental karyotypes

are

known

and a parental inversion is identified

.

If

parental karyotypes are

unknown i

n a suspected recombinant, the abnormal chromosome should be designed as a derivative chromosome (

der

).

Isochromosomes

(

i

)

An

isochromosome

is an abnormal chromosome with two identical arms due to duplication of one arm and loss of the other arm (mirror image of a chromosome from its centromere).

46,XY,i(6)(p10)

An

isochromosome

for the short arm of chromosome 6 has replaced one copy of chromosome 6.

46,X,i(X)(q10)

This is a female with one normal X chromosome and one

isochromosome

for the long arm of the X chromosome.

This

karyotype is a frequent finding in patients with Turner syndrome

Isoderivative

Chromosomes (

ider

)

An

isoderivative

chromosome designates an

isochromosome

formation for one of the arms of a derivative chromosome.

46,XY,ider(22)(q10)t(9;22)(q34.1;q11.2)

This is an

isoderivative

chromosome comprised of the long arm of the “Philadelphia chromosome.” It is one of the most common

isoderivative

chromosomes seen in cancer

cytogenetics

Dicentric

(

dic

),

Isodicentric

(

idic

) Chromosomes

These are structurally altered chromosomes

with two centromeres.

In the karyotype description, both

dicentric

and

isodicentric

chromosomes are counted as

one chromosome

without the need to indicate the missing normal chromosome(s).

45,XY,dic(14;14)(q11.2;q32

)

This represents a

dicentric

chromosome formed

by breakage

and reunion at bands 14q11.2 and 14q32 on

the two

homologous chromosomes 14. However, if a

dicentric

chromosome

is proven to originate through breakage

and reunion

of sister chromatids, it may be designated as

dic

(

14

) (

q11.2q32).

Additional Material of Unknown Origin (add)

The triplet “add” is used to describe material of

unknown

origin attached to a chromosome region or band

. The material may have come from the same chromosome or another chromosome, and no known mechanism is implied .

46,XX,add(5)(q13)

Material of indeterminate origin is present on chromosome 5 at band q13.

Marker Chromosomes (mar)

abnormal chromosomes a plus sign is always used when describing the presence of a marker in the karyotype, and marker chromosomes are usually listed last in the nomenclature string.

If multiple markers can be distinguished as distinct from one another, they should be written as +mar1, +mar2; otherwise, +2mar should be used.

49,XY

,+8,+2mar

An additional copy of chromosome 8 is present, as are

two marker chromosomes.

Incomplete Karyotypes (

inc

)

Every attempt should be made to describe all aberrations in an abnormal cell or clone. However, when this is not possible (such as when

chromosome morphology is poor

), the triplet “

inc

” is placed at the end of the nomenclature string, after the description of the

identi

fi able abnormalities:

46,XY,del(7)(q22),

inc

[10]

a deletion involving the long arm of chromosome 7. The triplet “

inc

” indicates that other abnormalities are also present but cannot be described.

Parental Inheritance

When parental inheritance is known, the triplet “mat” for maternally inherited or “pat” for paternally inherited should be used, immediately following the designation of the abnormality.

If multiple different aberrations are inherited from the parents, the parental origin should be designated for each individual aberration even if both aberrations came from the same parent. If the parental chromosomes are normal with respect to the abnormality, the abnormality may be designed as “

dn

” for

de novo.

46,XX,t(8;9)(q13;p13)mat,

inv

(13)(q14q32)mat

Both aberrations were inherited from the mother.

46,XX,t(8;9)(q13;p13)mat,

inv

(13)(q14q32)

dn

The translocation was inherited from the mother and the inversion arose

de novo

.

Fragile Sites (

fra

)

Chromosomal fragile sites are inherited in a codominant Mendelian fashion and are commonly considered to be normal variants with no phenotypic consequences. Fragile sites have been known to be associated with a specific disease or phenotype, such as the

fragile X syndrome

.Regardless of their biological consequences, fragile sites are denoted by the triplet “

fra

,” for example,

fra

(X)(q27.3).