Learning Objectives1. Able to define Karyotyping2. Able to enumerate the steps in karyotyping3. Be familiar with basic terminologies like

aneuploidy, polyploidy, genetic sex, gonadal sex, phenotypic sex

4. Able to classify chromosomal disorders5. Able to enumerate and identify the clinical

features of Down’s syndrome, Turner’s syndrome and Klinefelter’s syndrome in photographs

Able to define hermaphroditism and pseudohermaphroditism

Able to list down the causes for male pseudohermaphroditism and female pseudohermaphroditism

KARYOTYPING

It’s a process of arranging each pair of homologous chromosomes in a sequence, the longest chromosomes being placed at the beginning and the shortest at the end.

Photograph

Manually Electronic device

Symbols used in describing a Karyotype A– G – Chromosome groups 1—22 – Autosome numbers

XY – Sex chromosome del – Deletion inv – Inversion P – short arm of chromosome Q – long arm of chromosome t-Translocation r-Ring chromosome

A,B,C,D,E,F,G depends on chromosome length- A longest- G shortest

Groups within these letters depend on the p/q ratio

ARMREGIONBANDSub-BAND, numbering from the centromere progressing distad

Chromosomal abnormalities

• Numerical Structural

• Aneuploidy Polyploidy

• Monosomy Trisomy Triploidy Tetraploidy

Syndromes Embryo usually Turner Down aborts Edwards Klinefelter’s

Structural abnormalities

• Deletion Inversion Duplication Insertion

Translocation

Aneuploidy Diploid chromosome number of a cell is not

an exact multiple of it’s haploid number ( i.e. 45, 47 in human cells ) - due to non-disjunction of chromosomes at

anaphase Polyploidy Chromosome number exceeds the diploid

number and is an exact multiple it’s haploid number ( 69, 92, etc. in human cells )

- failure of cytokinesis at the time of cell division & multiple gametic fertilization

Karyotype of trisomy 21

TerminologiesChromosomal sex –

• Describes X and/or Y complement – Determined at fertilization

• Presence of Y chromosome means testes development will occur irrespective of number of X chromosomes

• Gonadal sex –• Refers to tissue assigned as testis or ovary –

Embryonic gonad is bipotential i.e. can develop into either ovary or testis depending on gene expression( from 42nd day of gestation)

• SRY gene – expressed transiently in cells destined to become Sertoli cells and serves as a pivotal switch to establish the testis lineage

•  Ovarian development once thought to be default process

• Certain genes expressed in ovarian development (e.g., WNT4, R-spondin-1 – Impair testes development)

• Phenotypic sex –

• Refers to the structures of the external and internal genitalia and secondary sex characteristics

• The male phenotype requires the secretion of AMH/MIS from Sertoli cells – And testosterone from testicular Leydig cells

AMH – Mullerian duct regression (from 60–80 days gestation)•

Testosterone – Wolffian structure development ( Vas, seminal vesicles ,epididymides) 60-80 days

DHT – promotes development of male external genitalia ( 65- 100 days)

• Sexual ambiguity is present whenever there is disagreement among these various criteria for determining sex.

Female pseudohermaphroditism• Genetic sex – 46 XX• EXCESS FETAL ANDROGENS - Congenital adrenal hyperplasia EXCESS MATERNAL ANDROGENS - Maternal androgen secreting tumors (Ovary,

adrenal) - Maternal ingestion of androgenic drugs – testosterone, synthetic progestins, minoxidil,

phenytoin sodium, streptomycin

Male pseudohermaphroditism• FAILURE TO PRODUCE TESTOSTERONE Pure XY gonadal dysgenesis ANATOMICAL TESTICULAR FAILURE Testicular regression syndrome

FAILURE TO UTILISE TESTOSTERONE 5-alpha reductase deficiency androgen receptor deficiency