Hereditary and environmental influences on Development

Chapter 9

Structure of Genes and Chromosomes

• All human somatic cells contain 46 chromosomes arranged as 23 pairs.

• There are 22 pair of autosomes and one pair of sex chromosomes

• Chromosomes are composed of genes and genes are composed of DNA

continued• DNA (hereditary material) is the

basic building block of genes and chromosomes

• DNA has three units: 1.Sugar(deoxyribose)

• 2. Phosphate group• 3. One of four nitrogen

bases(adenine,thyamine,guanine,and cytosine)

• If the sequence of nitrogen bases in the DNA is incorrect or if some bases are missing or added , a defect in body structure or function may result

Genes• Gene is a segment of DNA that

directs the production of a specific product needed for body structure or function

• Contain coded information that determine person’s unique characteristics

• Human probably have between 30,000 to 40,000 genes in each cell

Continued• Each person has two genes for

every trait• Genes that code for the same

trait have two or more alternate forms(alleles)

• Mutation often involve change in agene that harms function ,such as abnormal hemoglobin in sickle cell anemia

Transmission of single traits by single gene

• Inherited characteristics are passed from parents to child by genes in each chromosome

• Traits are classified whether they are Dominant or recessive and whether its located on autosomes or sex chromosomes

Alleles• Because human have a pair of

matched chromosomes ,they have one allele for agene at the same location on each member of the chromosome pair

• The paired allele may be Identical (homozygous) or different (heterozygous)

• A new trait may emerge because of a change in the genes within the gametes

• The off spring who receive the new version will have it in all somatic cell and can transmit it to further generation

• Dominant gene: one copy is enough to cause the trait to be expressed

• Recessive Gene: two identical copies are needed for the trait to be expressed

• Some alleles are equally dominant such as blood group A and B

Patterns of Single gene Inheritance

• Autosomal Dominant

• Autosomal recessive

• X- linked

• See table (9-1) for summary of characteristics and transmission

Autosomal Dominant Traits

• Produced by dominant gene on a none Sex chromosome

• A single copy of the gene is enough to produce the trait so the person usually affected

• Occasionally , a person receives two copies of the same abnormal dominant gene, such individual is usually much more severely affected

• Males and females are equally likely to have the trait

• Often appears in every generation of family

• A parent with the trait has a 50% chance of passing the trait to the child

Examples of Autosomal Dominant Traits and

Disorders• Normal traits: blood group A and B,

Rh positiveAbnormal traits(disorders):

Huntington’s disease• Neurofibromatosis• Dwarfism• Polydactyl• Poly cystic kidney disease

Autosomal Recessive Traits

• Person receive two copies of a recessive gene carried on outosomes

• Males and females are equally likely to have the trait

• Situations that increase the risk of occurrence:1. close blood relation ships(consanguinity) of the parents

2. groups isolated by geography ,culture religion or other factors

• Children of carrieries have:

• 1. 25% chance for receiving both copies of defective gene and thus having the disorder

• 2. 50% chance of receiving one copy of gene and being carriers like their parents

• 3.25% chance of receiving both copies of normal gene (neither carrier nor affected)

Examples of Autosomal Recessive Traits and Disorders

• Abnormal disorders: • Tay-sachs disease (fatal genetic lipid storage

disorder)• Sickle cell• Cystic fibrosis (an autosomal recessive genetic

disorder that affects mostly the lungs but also the pancreas, liver)

• Phenylketonurea• Normal traits: blood group O and RH negative

•

X-Linked Recessive• Only one copy of the gene is needed to

cause the disorder in the male• Male are affected, with rare exception• Females are carriers of the traits• Female can show full disorder in two

circumstances:• 1. If the female has a single X

chromosome (Turner's syndrome)• 2. When female child is born to an

affected father and carrier mother

• Affected males are related to one another through carrier females

• Affected males don't transmit trait to their sons

• Males who is affected transmit the gene to 100% of their daughter not their sons

• Sons of carrier female have 50% chance of being affected and 50% not affected

• Daughters of carriers female have 50% chance of being neither affected nor carrier

• New X- linked genes may rise by mutation

• Example:Color blindness

• Hemophilia (bleeding disorder that slows the blood clotting process)

Chromosomal Abnormalities

• Numerical abnormalities

• Structural abnormalities

Numerical Abnormalities

• Trisomy

• Monosomy

• Polyploidy

Trisomy• Exists when each body cell contains

extra copy of one chromosome ,so the total number of chromosome is 47

• Results from non-disjunction• The most common example is Down

Syndrome or Trisomy 21• Incidence increase with maternal age• Down syndrome is an example of

trisomy of autosomes

Continued Trisomy• Another example of trisomy but in sex

chromosomes is Klinefelter’s Syndrome or trisomy of sex chromosome (XXY)

• This syndrome affects only male• Affected male has an extra X

chromosome• Affected male exhibits poorly

secondary sexual characteristics and small testes,usually infertile

Monosomy• Occurs when each body cell has

missing chromosome ,total # 45• The only example compatible with life

and consider Sex chromosome abnormality is Turner's Syndrome or Monosomy X

• Affect only female• Affected female have single X

chromosome• Have undeveloped secondary sexual

characteristics and undeveloped ovaries

Polyploidy• Occurs when gametes do not

halve their chromosome number during meiosis and retain both number of the pair or when two sperm fertilize an ovum

• The total number of chromosomes will be 69 or 92

• Polyploidy usually results in early spontaneous abortion

Structural Abnormalities• May result from

• 1-deletion or addition of a chromosome

• 2-rearangement of DNA within a chromosome

• 3 - Translocation: part or all of chromosome is attached to another

• Example Fragile X syndrome • Cat’s cry syndrome

Fragile X Syndrome

• A site in chromosome X is more fragile than normal

• Although female might be affected but male are more severely affected

This syndrome is inherited in X linked dominant pattern

Cat’s Cry Syndrome

• Missing part of the short arm of chromosome number 5

• Characterized by mewing crying of a cat,microcephaly and mental retardation

Multifactorial Inheritance• Results from interaction of

genetics and environmental factors

• Characteristics:• - present and detectable at birth

• - isolated defects rather than ones occur with other unrelated abnormalities

• -may cause a secondary defect

Examples of Multifactorial disorders

• Many heart defects

• Neural tube defect

• Cleft lip and cleft palate

• Pyloric stenosis

Risk of occurrence of multifactorial Disorders

• Not associated with a fixed risk of occurrence or recurrence in a family

• Factors that may affect degree of risk• 1-number of affected close relatives• 2 -Severity of disorder in affected family

member\• 3-Sex of affected person• 4-Geographic location• 5-Seasonal variations

Environmental influences

• Teratogenes• Are agents in fetal environment

that either cause a birth defect or increase likelihood that a birth defect will occur

• Usually cause more than one defect which distinguish it from multifactorial disorders

Types of Teratogenes• 1-Maternal infectious agents such as

viruses and bacteria• 2. Drugs and other substances such as

tobacco and alcohol• 3. Pollutants and chemicals• 4. Ionizing radiation• 5. maternal hyperthermia• 6.Maternal disorders such as DM• See Box 9-1 selected environmental

substances that harm fetus

Prenatal Diagnostic Tests for Fetal Abnormalities

• Alpha Fetoprotein AFP

• CVS (chorionic villi sampling)

• Amniocentesis

• Ultrasonography

Genetic Counseling

• Provides services to help people understand disorders about which they are concerned and the risk that it will occur in their family

AFP• Is the main protein in fetal plasma• Might be measured from maternal

serum or from amniotic fluid• Best done between 16-18 GW• Elevated level of AFP indicates• 1. neural tube defect• 2. esophageal obstruction• 3. hydronephrosis

• Low level of AFP indicates: chromosomal Trisomies like Down syndrome

CVS• Microscopic projections from

the outer membrane (chorion)

• Used to diagnose fetal chromosomal abnormalities between 10- 13 GW

Amniocentesis• Aspiration of amniotic fluids from

amniotic sac• Early amniocentesis between 11-

14GW• Second trimester between 15-20 GW• Done to detect level of AFP and

analysis of cells for any chromosomal abnormalities

Ultrasonograghy

• Done to detect any organ’s abnormalities but not for chromosomal abnormalities