Pathophysiology: Chapter 21 Congenital and Genetic Disorders
Diagnostic tools
blood tests (alpha-fetoprotein test) ultrasounds In utero testing (amniocentesis/ chorionic villi assay) Neonate testing (Excreted metabolities ex. PKU) DNA testing
Multifactorial disorders?
Large number of disorders are of this type often have pattern of familial inheritance Environmental component
Designer drugs
Proteomics research Research will help develop drugs tailored to an individual genotype reduce unwanted side effects of commonly used medications
RNA
Provides the communication link with DNA during the actual synthesis of proteins and helps maintain control of cell activity.
Chromosomal disorders examples
down syndrome turner syndrome XO (only one sex chromosome) Klinefelter Syndrome XXY
TORCH
T- Toxoplasmosis O- Other (hepatitis B, mumps, rubeola, varicella, gonorrhea, syphillis) R- Rubella C- Cytomegalovirus H- Herpes
Gene penetration
frequency of expression of the gene among individuals carrying the gene
Familial tendency
The family members have an increased risk of developing the disorder, but not every family member will have the disease
Genotype
The genetic makeup of a cell or individual
Ultimate goal of genetic engineering
insert normal functioning allele to prevent disease
Other congenital or developmental disorders result from
premature birth, difficult labor, and delivery or exposure to damaging agent during fetal development
Mendelian inheritance includes
recessive and dominate patterns
amniocentesis
sampling of amniotic fluid to screen for developmental abnormalities in the fetus
Klinefelter Syndrome XXY
- Extra X chromosome is present - infertility
Turner syndrome XO (only one sex chromosome)
- affects females - short stature - infertility
Autosomes
22 pairs; Any chromosome that is not a sex chromosome
How many pairs of chromosomes are in each human cell?
23
Karyotype
A display of the chromosome pairs of a cell arranged by size and shape.
trisomy .
A genetic condition of having three chromosomes instead of two. The condition causes various birth defects.
mitosis
A nuclear division resulting in the production of two somatic cells having the same genetic complement as the original cell. (diploid)
Autosomal dominant disorder examples
Adult polycystic kidney disease Huntington's chorea Familial hypercholesterolemia Marfan's syndrome
What are teratogenic agents?
Agents that cause damage during embryonic or fetal development
Mendelian inheritance results can be predicted using
Algebra or Punnett squares
What is polygenic
Caused by multiple genes
What are the single-gene disorders?
Autosomal Recessive Autosomal Dominant X-linked Dominant X-Linked Recessive
Autosomal Recessive Disorders
Both parents must pass on the allele for disorder parents may be heterozygous and unaffected; they are termed carriers Parents may be homozygous and affected Male and female children are affected equally Homozygous recessive child has the disorder Heterozygous child: No clinical signs of disease and child is a carrier
Multifactorial disorder examples
Cleft palate congenital hip dislocation congenital heart disease Type 2 diabetes mellitus Anencephaly Hydropcephalus
X-linked Recessive disorder examples
Color blindness Duchenne muscular dystrophy Hemophilia A
Autosomal Recessive disorder examples
Cystic fibrosis PKU- lack of PAH Tay-sachs disease
anomaly
Deviation from what is normal (developmental abnormality)
Congenital anomalies?
Disorders present at birth
Phenotype
Expressions of genes; Appearance of individuals characteristics
X- linked Dominant disorder examples
Fragile X syndrome
homozygous
Having two IDENTICAL alleles for a trait
X- linked Dominant disorders
Heterozygous males and females can be affected Reduced penetration in females
Mendelian laws or patterns
Inheritance of many genes for both normal characteristics and disease characteristics follows specific patterns of inheritance
Autosomal Dominant Disorders
Inheritance of one allele causes disorder; only one parent needs to carry allele No carriers unaffected persons do not transmit the disorder some conditions become evident later in life allele for disorder may have been passed on to next generation termed delayed lethal genotype
Genetic engineering
Isolating, copying, and transplanting genes (EX.modified foods)
Fragile X syndrome
Most common cause of cognitive defects Effects are variable and related to the extent of mutation of the allele
Allele
One of two forms of a gene at corresponding sites on a chromosome pair; the code for phenotype or characteristic manifested in an individual.
organogenesis
Organ formation that takes place during the first two months of prenatal development.
Gene expression
Related to the cell's specific function
International Human Genome Project
Research directed toward mapping all the genes on a particular chromosome and identifying the role of each gene
Junk DNA
Sequences of genes with unknown functions
Inherited disorders may be caused by
Single- gene expressions Chromosomal defect Polygenic expressionis
Genetic disorders may result from
Single-gene trait chromosomal defect may be multifactorial
Characteristics of down syndrome
Small head, round face, flat facial profile slanted eyes and epicanthic fold large tongue and high arched palate small hands and single palmer crease short stature muscles tend to be hypotonic; loose joints delayed developmental stages cognitive impairment ranges from mild to major delayed or incomplete sexual development
Proteomics
Strives to characterize all of the proteins that are significant in the metabolic pathway for expression of a particular allele
What are single- gene disorders?
Trait controlled by one set of alleles transmitted to subsequent generations
Down Syndrome
Trisomy 21 common chromosomal disorder risk increase with maternal age
heterozygous
Two DIFFERENT alleles for a trait
Chromosomal anomalies
Usually caused by an error during meiosis, when DNA fragments are displaced or lost altering the genetic information
X-linked Recessive disorder
X-linked Recessive disorder Allele carried on the X chromosome but not the Y chromosome Manifested in heterozygous males lacking the matching unaffected gene on the Y chromosome heterozygous females are carriers homozygous recessive females may be affected inheritance may appear to skip generations
incomplete dominant
alleles which are not dominant to each other so that their characters either blend together or else produce a new phenotype that neither allele could produce by its self.[ex. red+ white=pink]
Mutation
alteration in genetic material which may be spontaneous or result from exposure to harmful substances. Ex. Radiation, chemicals, or drugs