Tài liệu tham khảo Sinh học Lớp 12

XO Turner Syndrome 
Features: 
Female phenotype 
Short stature 
Webbing of the neck 
Small, widely-spaced nipples 
XXY Klinefelter Synd . Features: 
Male 
Often unusually tall; long arms and legs 
Breast development 
Underdeveloped testes 
Hypophosphatemia : example of X-linked dominant inheritance 
Symptoms: short stature, bow-legs, lowered phosphate levels in blood 
males transmit trait to none of their sons and all of their daughters 
females transmit trait similar to autosomal dominant 
5 ft 
45, X0 – Turner syndromes 
http:// www.gfmer.ch/Genetic_diseases/Turner_syndrome/Turner.htm 
Total fetal 
hydrops 
normal intelligence; 
may have 3D spatial problems 
or math problems. 
99% of cases 
 – aborted 
1 in 2,500 or 
1 in 2,000 
liveborn females . 
yalenewhavenhealth.org /.../ topic.asp?hwid =zm2596 
Gynecomastia – 
Male with female features 
small testes, 
inability to produce sperm 
Mental retardation 
is related directly to the number 
of supernumerary X chromosomes 
(-15 IQ unit per 1 extra X). 
47, XXY – Klinefelter syndrome – or even 47, XXXY etc. 
1 out of 500 or 1000 males; 
 most go through life undiagnosed 
40% of embryos survive to birth 
Cleft Palate... 
In addition to needing plastic surgery to repair the opening, these children may have problems with their feeding and their teeth, their hearing, their speech, and their psychological development as they grow up. 
Medical and technology advances have been invaluable in the treatment of the cleft lip and palate. Clefts occur 1 time in 1,000 births in Caucasians, more often in Asians and Native Americans, and less often in African Americans. 
Fetal Alcohol Syndrome... 
Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) are growing problems in the United States. Despite the warnings posted in bars and restaurants and the increased media attention given to the perils of alcohol use during pregnancy, the rate of drinking among women of childbearing age continues to rise. The incidence of FAS may be as high as 12,000 per year, with FAE evident in up to 36,000 infants per year. Drinking during pregnancy affects not only the mother, but also the growing fetus. Alcohol can cause physical deformities and neurobehavioral deficits in the infant and growing child. Thus, it is not surprising that FAS is the leading cause of mental retardation and the only one that is preventable. 
ANY consumption of alcohol during ANY time during the gestation period can damage a baby’s brain. 
For example, sickle-cell disease is caused by a mutation of a single base pair in the gene that codes for one of the polypeptides of hemoglobin. 
A change in a single nucleotide from T to A in the DNA template leads to an abnormal protein. 
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings 
FISH analysis (Fluorescent in situ hybridization) -- translocation 
mti-n.mti.uni-jena.de/~huwww / MOL_ZYTO/imageAU9.JPG 
FITC or Fluorescein (green), 
Texas-red (red), 
Rhodamine (red), 
DAPI (blue) 
COMMON FLUORO DYES 
Green + RED = YELLOW 
FISH analysis (Fluorescent in situ hybridization) --DELETION 
http:// lambertlab.uams.edu/images/cell.jpg 
Two green, two reds 
on different chromosomes 
– no deletion 
Two green, one red – 
One red is deleted . 
Interphase FISH, relaxed chromatin 
Size of deletion can not be estimated. 
Deletion size is smaller 
than distance to green signal (probe) 
GREEN SIGNAL SERVE AS A CONTROL PROBE 
ON A SAME CHROMOSOME. 
The First HapMap Success Story:Age-Related Macular Degeneration 
Two other risk variants have 
been identified in the last two months. 
Together these account for 74% 
of risk, and point to powerful 
new approaches to prevention 
and treatment. 
XY sex determination 	 X-Y chromosomes 
autosomes 
SRY locus 
Described in text, p. 283 
All patients with same diagnosis 
All patients with same diagnosis 
Grey: Normal responder. 
Orange: Toxic responder. Blue: Non-responder. 
Treat with conventional 
drug or dose 
 Responders and patients 
 not predisposed to toxicity 
All patients with same diagnosis 
Treat with alternative 
drug or dose 
non-responders 
and toxic responders 
Evans, Johnson. Annu Rev Genomics Hum Genet 2001. 
Dosage Compensation Mechanism for X-Linked Genes in Mammals 
1.	Gene dosage varies between the sexes in mammals, because females have two copies of X while males have one. Early in development, gene expression from the X chromosome must be equalized to avoid death. Different dosage compensation systems have evolved in different organisms. 
2.	In mammals, female somatic cell nuclei contain a Barr body (highly condensed chromatin) while male nuclei do not. The Lyon hypothesis explains the phenomenon: 
a.	Barr body is a condensed and (mostly) inactivated X chromosome. Lyonization of one chromosome leaves one transcriptionally active X, equalizing gene dose between the sexes. 
b.	An X is randomly chosen in each cell for inactivation early in development (in humans, day 16 postfertilization ). 
What is unusual about the following pedgree ? 
Males pass on the trait to all males: holandric , or Y-linked inheritance 
Only males are affected 
But affected males do not transmit trait to all sons 
trait can be transmitted via females 
An example of SEX-LIMITED trait: inherited as an autosomal dominant, but only one sex shows trait 
Example: Precocious Puberty 
Sex-Limited Traits 
Fetal Alcohol Syndrome... 
Facial characteristics that suggest the diagnosis of FAS. 
The rarest form of spina bifida is when the spinal tissue actually protrudes from the body. This only occurs in 10% of all cases. 
Spina Bifida... 
Various degrees of leg and foot deformities are found in spina bifida patients, depending on the size of the improper spinal closure. 
Hydrocephalus... 
Normally within the brain there are some cavities named ventricles, where a liquid known as Cerebrospinal Fluid (CSF) is produced. The purpose of this is to protect the brain and spinal cord, acting as a shock absorber. It also carries away disposed materials. The CSF circulates from the ventricles towards a space that exists between the brain and the membranes ( meninges ) that surround it, from where it is "eliminated", into the blood stream. 
In the individual with hydrocephalus, the fluid does not drain away properly, but accumulates. 
In an infant, the seams of the skull have not yet fused, so the skull gets bigger as the fluid accumulates. 
DNA Methylation and Cancer 
Robertson KD. DNA methylation and human disease. Nat Rev Genet 2005 
Dynamic Domains 
Kosak ST. Gene Order and Dynamic Domains. Science 2004 
Gleevec™ – Specifically Targets 
An Abnormal Protein, Blocking 
Its Ability To Cause Chronic Myeloid Leukemia 
Chromosome 9;22 
translocation 
CML 
Bcr - Abl fusion protein 
Gleevec™ 
Bcr - Abl fusion protein 
 Normal  
Multiple mutations lead to colon cancer Genetic changes --> tumor changes 
Cellular 
Tumor Progression