Quiz 1

Ref: Nobelprize.org
 Nobel Prize on physiology medicine was based on a paper on cancer immunotherapy by James P. Allison and Tasuka Honjo. It describes their discovery of cancer therapy by inhibition of negative immune regulation.

Ref: Harrison 19th and who. int p 633
The question is replicated verbatim from Harrison, "Thalassemias are the most common genetic disorders in the world, affecting nearly 200 million people worldwide"

Ref: Harrison 20th edition, p 2972; Robbins 8th ed. p. 173, Harrison 19th p 439
 Gonadal mosaicism results from a mutation that occurs postzygotically during early (embryonic) development if the mutation affects only cells destined to form the gonads, the gametes carry the mutations, but the somatic cells of the individual are completely normal. Such an individual is said to exhibit germ line or gonadal mosaicism.
 A phenotypically normal parent who has germ line mosaicism can transmit the disease-causing mutation to the offspring though the mutant gamete.
 Since the progenitor cells of the gametes carry the mutations, there is a definite possibility that more than one child of such a parent would be affected. It is seen with tuberous sclerosis and osteogenesis imperfecta.

Ref: Harrison 20th edition, p 3478; Harrison 19th p 437, 850
In contrast to the homologous pair recombination that takes place in the nucleus, mtDNA molecules do not undergo recombination, and so mutational events represent the only source of mtDNAgenetic diversification. Moreover, with very rare exceptions, it is only the maternal DNA that is transmitted to the offspring. The fertilized oocyte degrades mtDNA carried from the sperm in a complex process that involves the ubiquitin proteasome system. Thus, whereas mothers transmit their mtDNA to both their sons and their daughters, only the daughters are able to transmit the inherited mtDNA to future generations. Accordingly, mtDNA sequence variation and associated phenotypic traits and diseases are inherited exclusively along maternal lines.

Ref: Harrison 20th edition, p 2973; Robbins 7th edition pg 155-6, Table 5.5 174, Harrison 19th p 2510
Chromosome breakage syndromes are associated with high level of chromosomal instability. Such conditions include. Fanconi anemia, Bloom syndrome, Ataxia telangiectasia. Ehlers-Danlos syndrome (EDS):
 Genetic disorder resulting from defective synthesis of fibrillar collagen
 Skin is extraordinary stretchable, extremely fragile and vulnerable to trauma, joints are hypermobile
 Internal complications: rupture of colon, large arteries

Ref: Robbins: 9th edition ch 5, pg, 161, Harrison 19th p 83e-1
 Down's syndrome is the most common of the chromosomal disorders and is a major cause of mental retardation characterized by meiotic non- disjunction.
 FISH with chromosome 21-specific probes reveals the extra copy of chromosome 21 in such cases. Most have normal chromosome numbers, but the extra chromosomal material is present as a translocation.

Ref: Rudolph paediatrics 22nd edition p 2070
 Mosaicism involving the Y chromosome occurs in 5%.
 Gonadoblastoma among Y-positive patients occurred in 7-10%.
 The current recommendation that prophylactic gonadectomy should be performed even in the absence of MRI or CT evidence of tumors
 The gonadoblastoma locus on the Y chromosome (GBY) maps close to the Y centromere.