From one parent, one inherits

autosomal chromosomes and one sex chromosome

This number of chromosomes is known as the

The diploid number is

The chromosome looks like an X shape during

The point of attachment of the sister chromatids is the

If it is exactly in the middle, it is called metacentric

If it is just off centre, it is called

If the centromere isn't in the middle it's called

with the small ends of the chromatids called satellites

The female karyotype is represented as

When they are stained, chromosomes become banded, the short arm is called p and the long arm is called

Images are done with fluorescent in-situ hybridisation

There are different types of chromosomal abnormalities:

Loss or gain of a chromosome:

Structural - translocations, deletions, insertions, inversions, rings

Mosaicism- different cell lines

Trisomy 21:

Overall incidence is 1 in 650. Strong association between incidence and advancing

Clinical features include:

Newborn period - severe hypotonia, sleepy, excess nuchal skin

Craniofacial - macroglossia:

small ears, epicanthic fold, upward sloping palpebral fissures, brushfield spots

Limbs - single palmar crease, wide gap between first and second toes

Cardiac - atrial and ventricular defects

They present with IQs of 25-75 and in terms of mood are generally

and their social skills are relatively

They have increased of leukaemia and

It is caused by trisomy 21 in 95% of all cases, 4% are caused by a

with the breakage of the acrocentric chromosomes and fusion of their long arms

1% is caused by mosaicism, children are less affected

Monosomy X:

Incidence in 1 in 3000 female births, can be detected in the 2nd trimester where generalised oedema and swelling in the

can be seen. They look normal at birth or look puffy.

Low posterior hairline, short 4th metacarpals, webbed neck, aorta defect, normal intelligence

In adults their stature is

and they have ovarian failure

Treated with

replacement for secondary sexual characteristics and prevention of osteoporosis

Caused by a loss of the X or Y chromosome in

in 80% of cases, can also be causes by ring chromosome, single arm deletion, mosaicism

Dosage compensation is different in sex chromosomes as only one X is required so the other is switched off in females

Polysomy X in females: 1 in 1000 have 47,XXX with a 10-20 point decrease in IQ but no physical abnormalities

95% have an extra maternal X arising in

They have normal fertility, there are also 48,XXXX and 49,XXXXX these result in

Polysomy X in males: 47,XXY-

1 in 1000 live male births, clumsiness, verbal learning disability, taller than average, 30% develop gynaecomastia, infertile, increased risk of leg ulcers

The extra X can come from male or female

It is possible to be chromosomally one gender and

the other gender. The gene that causes development of the testes is the

This can be translocated to the X chromosome in recombination

XX males develop testes but are infertile because some genes are needed for spermatogenesis

Di George syndrome: Variable symptoms-

Congenital heart disease, palatal abnormalities

characteristic faces, learning difficulties

Commonest disorder caused by

1 in 4000 births

Cri du chat syndrome

Characteristic facies: Microcephaly, hypertelorism, micrognathia, epicanthal folds, low-set ears, hypotonia, severe

characteristic cry in babies like a

Most inborn errors of metabolism are autosomal

or X-linked. The defective proteins are mainly enzymes.

The UK newborn screening programme screens newborns for Phenylketonuria, congenital hypothyroidism, sickle cell disorders, cystic fibrosis and

Phenylketonuria: caused by deficiency of the enzyme

which causes phenylalanine to accumulate, this is converted into phenylpyruvate, which is excreted into the urine

It also causes a tyrosine deficiency leading to reduced

It manifests with severe mental retardation and convulsions

Phenotypically people have blonde hair, blue eyes and eczema

MCAD: commonest disorder of fatty acid oxidation

deficiency of the enzyme medium-chain

Causes episodic hypoketoic hypoglycaemia and presents as early as 3 months, can present as a coma, metabolic acidosis and encephalopathy

Sudden death can occur- 25% death rate in undiagnosed cases

The enzyme causes dehydrogenation of the acyl-coA species in the beta-oxidation cycle in

metabolism so these people can't break these fats down, they accumulate.

It is treated by maintaining an adequate

intake to prevent the switch to fatty acid metabolism

Chromosome rearrangements can lead to gene copy number changes via deletion or

They can also cause gene fusion via translocation or

Most tumour supressor gene require inactivation of

allele(s) to cause malignancy. The first mutation is often caused by a mutation and the second is usually caused by a

The first mutation usually reduces the transcription level but is insufficient to produce a phenotypic effect. The second allele needs to be inactivated also which causes a total loss of

for the malignant phenotype to be conferred. Some only need one allele to be affected - haploinsufficiency

LOH - loss of

has several related meanings:

A historical method of assessing the stability of cancer genomes and looking for the location of TS genes, another term for deletion and unmasking of the mutated copy of a TS gene. LOH describes a region of apparent

probably via a deletion in cancer tissue that may mark the location of a

99% of cancers aren't

The vast majority of cancers are caused by acquired changes in

tissue, there are very few cancers that are initiated from one parent, or sometimes both, of a mutation in gremlin tissue. In inherited cancers, the risk of cancer is

2-4% of breast cancer cases are caused by a germline mutation of BRCA1 and BRCA2 gene

60% of these are at risk of developing cancer by age 90 and their average of onset is

than those without germline mutation. The inactivation of the second allele is usually by a somatic

There is also an increased risk of developing

cancer, BRCA2 mutations also predispose men to breast cancer. The mutations can occur

in the BRCA exon structure. They result in a non-functional protein.

BRCA1 and BRCA2 normal function is

via a process called homologous recombination. A truncated or non function protein causes impaired DNA repair.

Acquired chromosome abnormalities are sporadic

Disease markers in patient management are oncogenic

Cancer genomes have cytogenetic changes as well as molecular changes associated with them. These cancers can be causal or

during disease progression. Haematological malignancies - lymphomas and

A clonal myeloproliferative disorder of the pluripotent haematopoietic stem cell leading to an overproduction of mature granulocyte is chronic

It is triphasic with a chronic stage, an accelerated stage and a terminal acute stage.

The hallmark for CML is the BCR-ABL1 fusion gene which resides on the Philadelphia chromosome and codes for tyrosine kinase

To treat this, a tyrosine kinase inhibitor like

But 20-30% patients lose response and require a second tyrosine kinase inhibitor.

Genetic methods can be used to detect leukaemia like:

Conventional cytogenetics - To look for the

chromsome via G-banding karyotypes.

Fluorescent in-situ hybridisation - look for juxtaposition of BCR and ABL

PCR

The abnormal accumulation of immature granulocytes called promyelocytes is acute

Characterised by a chromosomal

in the retinoid acid receptor gene and the promelocytic leukaemia gene on chromosome 15