CSU MIP 315A - lecture 28_29(1)(1) (1)-1-1 (83 pages)

Previewing pages 1, 2, 3, 4, 5, 6, 38, 39, 40, 41, 42, 78, 79, 80, 81, 82, 83 of 83 page document View the full content.
View Full Document

lecture 28_29(1)(1) (1)-1-1



Previewing pages 1, 2, 3, 4, 5, 6, 38, 39, 40, 41, 42, 78, 79, 80, 81, 82, 83 of actual document.

View the full content.
View Full Document
View Full Document

lecture 28_29(1)(1) (1)-1-1

48 views


Pages:
83
School:
Colorado State University- Fort Collins
Course:
Mip 315a - Human and Animal Disease
Human and Animal Disease Documents
Unformatted text preview:

Objectives Lectures 28 and 29 Explain the mechanisms and importance of gene transcription and translation Describe the forms and consequences of mutations Describe the etiology and pathogenesis of Turner s and Kleinfelter s syndromes Describe the etiology and symptoms of Down s syndrome Describe the pathogenesis of fetal alcohol syndrome Describe the etiologies and pathogenesis of Lesch Nyhan disease and 5 alpha reductase deficiency Darwin 1809 to 1882 More individuals are produced each generation that can survive Phenotypic variation exists among individuals and the variation is heritable Those individuals with heritable traits better suited to the environment will survive Mendel 1822 1884 Principles of heredity Peas Mendel s results Mendelian genetics Griffith 1928 Watson and Crick 1953 Watson and Crick 1953 Central dogma Proteins catalysis Catalysis Genetic Imprinting Mutation Nondisjunction Development Infant Mortality Infant Mortality 2012 Number of infant deaths 24 586 Leading causes of infant deaths Congenital malformations deformations and chromosomal abnormalities Disorders related to short gestation and low birthweight Sudden infant death syndrome Infant Mortality Infant Death Rate U S Falls Behind 68 Countries According To Save The Children Huffington Post April 2013 https www cia gov li brary publications the world factbook rankor der 2091rank html Congenital Defects Leading cause of defects is genetic change Inherited Teratogens Developmental malformations Chromosomal abnormalities Autosomal abnormalities Sex Chromosome Abnormalities Trisomy 21 Down s syndrome Trisomy 21 Trisomy 21 Life expectancy for people with Down syndrome has increased dramatically in recent decades from 25 in 1983 to 60 today Down syndrome is the most commonly occurring chromosomal condition Approximately one in every 700 babies in the United States is born with Down syndrome about 6 000 each year Letourneau et al 2 show that genomic domains that are normally associated with low or high levels of gene expression are respectively up or downregulated in a person with Down s syndrome compared with their identical twin who does not have the condition The result is a genome wide flattening of gene expression Occurrence is strongly dependent on maternal age 15 29 years 1 case in 1500 live births 30 34 years 1 case in 800 live births 35 39 years 1 case in 270 live births 40 44 years 1 case in 100 live births Older than 45 years 1 case in 50 live births Genes suspected in trisomy 21 Superoxide Dismutase SOD1 overexpression may cause premature aging and decreased function of the immune system COL6A1 overexpression may be the cause of heart defects ETS2 overexpression may be the cause of skeletal abnormalities CAF1A overexpression may be detrimental to DNA synthesis Cystathione Beta Synthase CBS overexpression may disrupt metabolism and DNA repair DYRK overexpression may be the cause of mental retardation CRYA1 overexpression may be the cause of cataracts GART overexpression may disrupt DNA synthesis and repair IFNAR the gene for expression of Interferon overexpression may interfere with the immune system as well as other organ systems Variations in trisomy 21 wide range of mental retardation and developmental delay Some babies are born with heart defects and others aren t Some children have associated illnesses such as epilepsy hypothyroidism or celiac disease and others don t The effect of overexpression of genes may depend on which allele is present in the person with trisomy 21 Sex Chromosome Abnormalities Turners Syndrome Coarctation Turner Syndrome In the US Frequency is approximately 1 in 2000 live born female infants As many as 15 of spontaneous abortions have a 45 X karyotype Mortality may be increased in the neonatal period because of coarctation of the aorta and in adulthood because of cardiovascular disease particularly aortic dissection Race No racial or ethnic predilections are known No associated Mental retardation X Chromosome Absent X both X chromosomes in 46 XX people play a part in oogenesis and the development of the fetal ovaries In 46 XX individuals by the end of fetal development the ovaries contain as many as 7 million oocytes By puberty this number has dwindled to as few as 400 000 and by menopause fewer than 10 000 Without a second X chromosome millions of oocytes begin to die And they continue to throughout the pregnancy and for the first years of the child s life By age two there are no ova left and the ovaries degenerate into fibrous streaks In these women menopause happens before menarche Variants of Turner Syndrome as the zygote begins to grow nondisjunctions may occur with the sex chromosomes and one cell gets two X chromosomes and the other none then as the individual develops some of her cells are 45 X and others 46 XX Mosaic Other times nondisjunction creates mosaics with three different sex chromosome karyotypes some even including normal male and female karyotypes like 46 XY 45 X 46 XX or 45 X 46 XX 47 XXX cells all inside one person X Chromosome Long Arm q Short arm p More Turner Variants Whole pieces of the long arm called the q arm or chunks of the short arm called the p arm of the X chromosome can get left behind creating X chromosomes that don t do all that they normally do These coupled with one or more complete X chromosome can create karyotypes like 46 XXp 46XXq missing pieces of the p arm or the q arm 46XXr with a ring chromosome formed from a piece of the X chromosome 46 XXqi another abnormal form of the q arm and many many more The people with these karyotypes can range from normal females to females with hypoplastic underdeveloped ovaries to Turner syndrome females to females with vestigial streak ovaries to females that look like males to males with dysgenic Klinefelter s Klinefelter Syndrome In the US over 3 000 affected males are born yearly In general severity of somatic malformations in Klinefelter syndrome is proportional to the number of additional X chromosomes mental retardation and hypogonadism are more severe in 49 XXXXY than in 48 XXXY Mortality rate is not significantly higher than in healthy individuals Most males born with Klinefelter syndrome go through life without being diagnosed Sex Chromosome Abnormalities People with Klinefelter syndrome may also have more than one extra chromosome resulting in genotypes which include XXYY XXXY and XXXXY Other mutations result in males that have an extra Y chromosome and a genotype of XYY These males


View Full Document

Access the best Study Guides, Lecture Notes and Practice Exams

Loading Unlocking...
Login

Join to view lecture 28_29(1)(1) (1)-1-1 and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view lecture 28_29(1)(1) (1)-1-1 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?