Quiz 2

Ref: Robbins: 9th edition p 456
In vertebrates, HOX (homeobox) proteins have been implicated in the patterning of limbs, vertebrae, and craniofacial structures.

Ref: Robbins & cotran: 9th, ch. 9, p 446, Nelson 19th Ch-74
 Prader-Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyper-ghrelinaemia and increased insulin sensitivity.
 Ghrelin is produced in the stomach and in the arcuate nucleus of the hypothalamus. It is the only known gut hormone that increases food intake (orexigenic effect).
 Gut peptides act as short-term meal initiators and terminators. They include ghrelin, PYY, pancreatic polypeptide, insulin, and amylin among others.
 Ghrelin levels rise before meals and fall between 1 and 2 hours after eating. In obese individuals the postprandial suppression of ghrelin is attenuated and may contribute to overeating.
 Rare genetic disorder with defect on chromosome 15
 The variety of symptoms can range from poor muscle tone during infancy to behavioral problems in early childhood.
 In Childhood: Delayed milestones/intellectual delay, Excessive sleeping, Strabismus, Scoliosis, Cryptorchidism, Speech delay, Poor physical coordination.
 Hyperphagia begins between the age of 2 and 8, and continues on throughout adulthood leading to obesity.

Ref Robbin's 9th edition p 158 ch, 5
 Karyotyping is the basic tool of the cytogeneticist. The usual procedure to examine chromosomes is to arrest dividing cells in metaphase with mitotic spindle inhibitors (e.g., N-diacetyl-N-methylcolchicine [Colcemid]) and then to stain the chromosomes. In a metaphase spread, the individual chromosomes take the form of two chromatids connected at the centromere. A karyotype is obtained by arranging each pair of autosomes according to length, followed by sex chromosomes.

Ref: Robbins: 9th edition ch. 5, p 172, Nelson 19th p Table 76-13, p 409
 Prader-Willi syndrome is characterized by mental retardation, short stature, hypotonia, profound hyperphagia, obesity, small hands and feet, and hypogonadism.
 In 65%to 70% of cases, an interstitial deletion of band q12 in the long arm of chromosome 15, del (15) (q11.2q13), can be detected.
 In most cases the breakpoints are the same, causing a 5-Mb deletion. It is striking that in all cases the deletion affects the paternally derived chromosome 15.

Ref: Robbins 7th edition p 151, Harrison 19th p 432e-2t
Dominant negative affects occurs when a mutant polypeptide not only loses its own function but also interferes with the product of normal allele in a heterozygote, thus causing more severe effects than deletion or non-sense mutations in the same gene. Structure proteins that contribute to multimeric structures are vulnerable to dominant negative affect e.g. collagen. Seen in: Osteogenesis imperfecta, Ehler Danlos syndrome, Marfan's syndrome

Ref: Nelson 18th edition, chapter 82
 The interaction between genes and the environment is called epistasis.Epistatic effects could affect the expressivity of a trait as well as the penetrance.
 An example of this is G6PD deficiency where an individual could carry the altered gene and be deficient in the enzyme, yet would never have a hemolytic crisis unless exposed to an oxidative stress.

Ref: Harrison: 18th, 547-551
Gene transfer is a novel area of therapeutics in which the active agent is a nucleic acid sequence rather than a protein or small molecule. Most gene transfers are carried out using a vector or gene delivery vehicle because delivery of naked DNA or RNA to a cell is an inefficient process. More clear-cut success has been achieved in a gene therapy trial for another form of SCID, adenosine deaminase (ADA) deficiency. Other diseases likely to be amenable to transduction of haemopoietic stem cells (HSCs) include:
 Wiskott-Aldrich syndrome
 Chronic granulomatous disease
 Sickle cell disease
 Thalassemia