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