cytogen p2 2nd week

Autosomes

are assigned a number (1-22) based on

size.

sex chromosomes

are noted by the letters X and

Y.

Karyotype descriptions

convey the total number of

chromosomes, the sex chromosome complement, and a

description of any chromosome abnormalities present.

1970s

Chromosome Banding

and Identification Launched in the early ______

Chromosome Banding

and Identification

Allows for the identification of chromosomes not

only by length and centromere position, but also by

their their unique banding properties.

Characteristic regions and

bands

within a given

chromosome are observed when

banding techniques are used.

Chromosome regions

refer to

those areas lying between two

distinct landmarks and are divided

into bands.

Banding/staining methods

are used to detect specific

chromosome regions or abnormalities.

G-, Q-, and R-banding techniques

show bands distributed along the entire chromosome

C-, T-, or NOR-banding techniques

are used

to identify specific chromosome structures that are heritable

features.

Giemsa stain

produces specific banding patterns for each

pair of homologous chromosomes similar to Q-banding.

Q-banding

Giemsa stain produces specific banding patterns for each

pair of homologous chromosomes similar to

trypsin

the chromosomes are treated with ________to partially

digest the chromosome prior to being stained.

G-banding.

AT-rich (gene poor) regions stain darkly with _______.

fluorescent stain (quinacrine dihydrochloride)

produces

specific banding patterns for each pair of homologous

chromosomes similar to G-banding,

fluorescent stain (quinacrine dihydrochloride)

excellent for

identifying centromeric regions of chromosomes 3, 4, and 13,

some acrocentric chromosomes and the Y chromosome.

G-banding

A fluorescent stain (quinacrine dihydrochloride) produces

specific banding patterns for each pair of homologous

chromosomes similar to

Q-banding

AT-rich (gene poor) regions fluoresce brightly with.

R-banding

A staining method in which chromosomes are heated

in a phosphate buffer

R-banding

then stained to produce a

banding pattern that is the reverse of that produced

with G-banding.

C-banding

After barium hydroxide treatment, Giemsa stain is used to

stain constitutive heterochromatin close to the

centromeres and on the long arm of the Y chromosome.

C-banding

is used to identify dicentric chromosomes and

variations of constitutive heterochromatin.

T-banding

a Giemsa staining technique that stains the telomeres

(ends) and the centromeres of chromosomes.

NOR Staining

A staining method utilizing silver nitrate

NOR Staining

which

preferentially accumulates in the NORs located on the

stalks of the acrocentric chromosomes that contain

active ribosomal RNA genes

normal occurrence

Exchange of genetic material between sister

chromatids and homologous chromosomes is a

____________.

structural rearrangements

It is only when exchanges occur between non allelic

chromosomal regions that _________ result.

Balanced

No net loss or gain of genetic information

Balanced

Generally phenotypically normal

Unbalanced

Additional and/or missing genetic material

Unbalanced

Clinically affected

Familial Rearrangements

Structural rearrangements may pass through multiple

generations of a family.

De Novo Rearrangements

It is not known what has occurred at the molecular level

within the rearrangement, and there are no family

members with the rearrangement from whom inferences

can be made.

Dicentric Chromosomes

Any chromosome exchange in which the involved donor and

recipient chromosome segments each contain a centromere

will result in the formation of a chromosome with two

centromeres

Acentric” Chromosomes

Because the centromere is essential for chromosomal

attachment to the spindle and proper segregation,

chromosomes lacking this critical component are rapidly lost.

true acentric

chromosome

are never seen.

Isochromosomes

consists of two copies of the same

chromosome arm joined through a single centromere in such a

way that the arms form mirror images of one another.

monosomic

____________ for the genes within the lost arm

trisomic

____________for all genes present

on the isochromosome.

Ring Chromosomes

traditionally thought to form as a result of

breakage in both arms of a chromosome, with

subsequent fusion of the ends and loss of the distal

segments.

Deletion

A genetic aberration in which a part of a chromosome

or a sequence of DNA is left out during DNA replication.

Terminal deletions

Caused by a single break with loss of the segment distal to the

break.

Interstitial deletions

Result from two breaks in a chromosome, loss of the

intervening segment, and reunion of the breakpoints.

Monosomy 1p36

Deleted region: 1p36

Monosomy 1p36

Mental retardation, growth delay,

hypotonia, early puberty, deafness, eye

problems, cardiomyopathy, seizures

and/or abnormal EEGs, enlarged anterior

fontanel, deep-set eyes, flat nasal bridge,

orofacial clefting or palatal abnormalities,

pointed chin, ear abnormalities.

Wolf-Hirschhorn

Deleted region: 4p

Wolf-Hirschhorn

Mental and growth retardation,

microcephaly, hypertelorism, broad nasal bridge, downturned

mouth, cleft lip and/or palate, micrognathia, cryptorchidism,

hypospadias

Cri du chat

Deleted region: 5p

Cri du chat

Mental and growth

retardation, cat-like cry in

infancy, microcephaly, round

face, hypertelorism, down

slanting palpebral fissures.

Sotos

Deleted region: 5q35

Sotos

Cardinal features include intellectual disability,

overgrowth, and characteristic long, thin facies with a broad forehead, sparse

frontoparietal hair, and down-slanted palpebral fissures. Macrocephaly,

advanced bone age, behavior problems, hypotonia, feeding problems, renal

anomalies, scoliosis, and seizures are also seen

Williams

Deleted region: 7q11.23

Williams

Mental retardation, short stature,

supravalvular aortic stenosis, hypercalcemia, friendly disposition,

hoarse voice, periorbital fullness, stellate pattern in the iris,

anteverted nares, long philtrum, full lips

Potocki-Shaffer

Deleted region: 11p11.2

Potocki-Shaffer

Mental retardation, biparietal foramina,

brachycephaly, turricephaly, multiple exostoses, micropenis, and

minor facial dysmorphism including a high forehead, small

upturned nose with broad tip, downturned mouth.

Jacobsen

Deleted region: 11q24.1–11qter

Jacobsen

Mental and growth retardation,

trigonocephaly, strabismus, cardiac defects, digit anomalies,

thrombocytopenia

Langer-Giedion

Deleted region: 8q24.11–8q24.13

Langer-Giedion

Mental and growth retardation, multiple exostoses,

cone-shaped epiphyses, fine scalp hair, bulbous nose, prominent ears, simple

but prominent philtrum, loose redundant skin in infancy.

Angelman

Deleted region: Maternal 15q11.2–15q13.1 deletion complementary to

the 15q11.2–15q13 .1 microduplication syndrome

Angelman

Mental and growth retardation, frequent laughter,

ataxia and jerky arm movements, seizures, maxillary hypoplasia, deep-set

eyes, large mouth with protruding tongue, widely spaced teeth, prognathia.

Prader-Willi

Deleted region: Paternal 15q11.2–15q13.1

Prader-Willi

Mental and growth retardation, hypotonia and feeding

problems in infancy, later obesity associated with hyperphagia, narrow

bifrontal diameter, almond-shaped eyes, small hands and feet, hypogonadism,

skin picking

15q13.3 Microdeletion

Deleted region: 15q13.3

15q13.3 Microdeletion

Developmental delay with mild to moderate learning

disability, autism spectrum disorder, schizophrenia, epilepsy, seizures, digit

anomalies, and facial features that include hypertelorism, short philtrum, and

a thick, everted upper lip. Extensive phenotypic variability and incomplete

penetrance have been reported.

Rubinstein-Taybi

Deleted region: 16p13.3

Rubinstein-Taybi

Mental retardation, postnatal growth retardation,

hypotonia, broad thumbs and toes, cryptorchidism, abnormal facies with

downward-slanting palpebral fissures; heavy, highly arched eyebrows; long

eyelashes; prominent and/or beaked nose; hypoplastic maxilla with narrow

palate.

Miller-Dieker

Deleted region: 17p13.3

Miller-Dieker

Mental and growth retardation, lissencephaly,

microcephaly, bitemporal depression, long philtrum, thin upper lip, mild

micrognathia, ear dysplasia, anteverted nostrils.

Hereditary neuropathy with liability

to pressure palsies (HNPP)

Deleted region: 17p11.2 deletion complementary to

the CMT1A syndrome duplication

Hereditary neuropathy with liability

to pressure palsies (HNPP)

Asymmetric recurrent palsies precipitated by focal

pressure beginning in the second or third decade of life and electrophysiologic

findings of prolonged sensory motor nerve conduction.

Smith-Magenis

Deleted region: 17p11.2

Smith-Magenis

Mental retardation, behavioral problems,

hyperactivity, sleep disturbance, decreased pain sensitivity, short stature,

brachycephaly, midface hypoplasia, prognathism, fingertip pads, hoarse voice.

17q21.3 Microdeletion

Deleted region: 17q21.3 deletion complementary to the 17q21.2

microduplication syndrome

17q21.3 Microdeletion

Mental retardation/developmental delay, delayed

speech, friendly disposition, hypotonia, normal growth, epilepsy, heart

anomalies, renal/urologic anomalies, abnormal hair color or texture, and

typical facies with high broad forehead, ptosis, blepharophimosis, up-slanting

palpebral fissures, epicanthal folds, a tubular- or pear-shaped nose, prominent

ears

Alagille

Deleted region: 20p12.2

Alagille

Cholestasis, peripheral pulmonic stenosis, vertebral

arch defects, posterior embryotoxon, abnormal facies including deep-set eyes,

broad forehead, long straight nose, prominent chin, small low-set or

malformed ears.

DiGeorge

Deleted region: 22q11.2 deletion complementary to proximal 22q11.2

microduplication syndrome

DiGeorge

Learning disabilities, short stature, overt or submucous

cleft palate, velopharyngeal incompetence, prominent nose with squared nasal

root and narrow alar base, conotruncal cardiac defects, and psychiatric

disorders in some.

Phelan-Mcdermid

Deleted region: 22q13.3

Phelan-Mcdermid

: Moderate to severe developmental delay, severe

expressive speech delay, behavior disturbance, increased tolerance to pain,

hypotonia, normal to accelerated growth, dysplastic toenails, large hands, and

minor dysmorphic features including dolichocephaly, ptosis, abnormal ears,

pointed chin.

Kallmann

Deleted region: Xp22.3

Kallmann

Hypogonadotropic hypogonadism, eunuchoid habitus,

anosmia or hyposmia, bimanual synkinesis.

Ichthyosis (X-linked)

Deleted region: Xp22.3

Ichthyosis (X-linked)

Hypertrophic ichthyosis, corneal opacities without

impairment of vision.

Duplications

Implies the presence of an extra copy of a genomic

segment resulting in a partial trisomy.

pure duplication

Can be present in an individual as a________

pure duplication

uncomplicated by other imbalances or in combination with a

deletion or some other rearrangement.

tandem duplication

If the duplicated sections are adjacent to the original,

the process is known as

displaced

s if they are separated by non duplicated

regions, the duplication is said to be

Duplicated region: 3q26.3

Duplication 3q

A Cornelia de Lange-like phenotype that includes

mental retardation postnatal growth retardation, long philtrum, palate

anomalies, anteverted nares, clinodactyly, talipes, renal and cardiac

abnormalities.

7q11.23 Microduplication

Duplicated region: 7q11.23 duplication complementary to the 17q21.2

microdeletion syndrome

7q11.23 Microduplication

Cognitive abilities range from normal to moderate mental

retardation, but all have speech delay. Other features include autism, hypotonia,

heart defects, diaphragmatic hernia, cryptorchidism, and dysmorphic facial

features including a short philtrum, thin lips, and straight eyebrows.

Beckwith-Wiedemann

Duplicated region: 11p15.5 b (Paternal)

Beckwith-Wiedemann

Macrosomia, macroglossia, organomegaly,

omphalocele, ear creases, hypoglycemia, tumor susceptibility. Beckwith

Wiedemann patients with cytogenetic duplications are more likely to have

learning difficulties.

Pallister-Killian

Duplicated region: Mosaic tetrasomy 12p usually secondary to an

extra metacentric isochromosome

Pallister-Killian

Mental retardation, streaks of hyper- and

hypopigmentation, sparse anterior scalp hair, sparse eyebrows and eyelashes,

prominent forehead, protruding lower lip, coarsening of face with age.

Proximal 15q11.2 Microduplication

Duplicated region: 15q11.2 15q13.1a Complementary to Prader-Willi/

Angelman syndrome deletion region