Genetics

U.K. College of Nursing

Genes and Chromosomes

Each cell contains 23 pairs of matched chromosomes for a total of 46 chromosomes per cell.

One chromosome from each pair is inherited from each parent.

There are 22 pairs of autosomes, which control most traits in the body, and one pair of sex chromosomes, which determine gender and other traits.

Genes and Chromosomes

Some genes are dominant and their characteristics are expressed even if only on one chromosome.

Some genes are recessive and their characteristics will be expressed only if they are carried by both chromosomes in a pair.

Group Exercise

Human Variation

Punnet Squares

Visual representation of the principles of inheritance

Dominant trait--Capital letter

Recessive trait--Small letter

Male vs female trait/gene

Patterns of Inheritance

Autosomal DominantAutosomal RecessiveSex-Linked (or X-linked)

DominantSex-Linked (or X-linked)

RecessiveChromosomal

AbnormalitiesCongenital Anomalies

Autosomal Dominant

Trait appears in every generation (does not skip)

Both males and females are affected

Each pregnancy of an affected person has a 50% chance of producing an affected offspring

Autosomal Dominant Disorders

Disorders Huntington’s Disease Retinitis Pigmentosa Polycystic Kidney Disease Achodroplasia Marfan Syndrome

Autosomal Dominant Disorders- Marfan Syndrome

Autosomal Dominant Inheritance

Autosomal Dominant

Clinical Situation-- One parent is unaffected

One parent carries the defective gene for Marfan Syndrome

Draw the Punnet Square

Autosomal Dominant Punnett Square

Autosomal Recessive

Both parents are usually unaffected, but are carriers

Trait first appears only in siblings rather than in parents

Trait found equally in males and females

25% risk when both parents are carriers

Increased incidence with consanguinity

Autosomal Recessive

Disorders Phenylketonuria Fanconi’s Anemia Tay Sachs Disease Sickle Cell Anemia Cystic Fibrosis

Autosomal Recessive Inheritance

Autosomal Recessive

Clinical Situation Male carries the defective

gene for Tay Sachs disease

Female carries the defective gene for Tay Sachs disease

Draw the Punnett Square

Autosomal Recessive Punnett Square

X-linked Inheritance

Sex-Modified Traits - Dominant genes are expressed in both males & females but at differing frequencies Ex: Baldness - expressed as

dominant in males, but recessive in females, never as severe in females

X-linked Dominant

Very rareOften lethal in males

therefore few males present in the pedigree

Multiple miscarriages may be present

No carrier status, all individuals with the gene are affected

Trait appears in every generation

X-linked Dominant

Female children of affected males will all be affected (100% risk); no male to male transmission.

Homozygous females (both X chromosomes are affected) have a 100% chance of having an affected child of either sex.

Heterozygous females (only one X affected) have a 50% of having an affected child with each pregnancy.

X-linked Dominant Disorders

Hypophosphatemic Rickets

Fragile X Syndrome

Fragile X Syndrome

X-linked Dominant

Clinical Situation Male is affected with

hypophosphatemic rickets

Female is unaffected

Draw the Punnet square

X-linked Dominant Punnet Square

X-linked Recessive

Incidence of trait much higher among males in a kinship than among females

Trait cannot be transmitted from father to son

An affected male will pass the carrier status to all his daughters

Female carriers have a 50% risk of transmitting the gene to their offspring with each pregnancy

X-linked Recessive

Disorders Hemophilia A Duchenne’s Muscular

Dystrophy Color-Blindness

Duscenne’s Muscular Dystrophy

X-Linked Recessive Inheritance

X-linked Recessive

Clinical Situation Male is affected with

Hemophilia A

Female is normal (non-carrier)

Draw the Punnett SquareUse X1 for chomosome with

normal allele and X2 for chromosome with disease allele

X-linked Recessive Punnet Square

X-linked Recessive

Clinical Situation Male is normal

Female is a carrier of color-blindness

Draw the Punnett Square

X-linked Recessive Punnett Square

X-linked Recessive

Clinical Situation Male is affected with

Duschenne Muscular Dystrophy

Female is carrier of Duschenne Muscular Dystrophy

Draw the Punnett Square

X-linked Recessive Punnett Square

Genotype - The actual gene constitution of a given person.

Phenotype - The observable characteristics of a given person

Traits can be environmentally modified type 2 diabetes PKU

Traits can be medically modified Sickle cell disease (bone marrow

transplant) Polycysitc kidney disease (kidney

transplant)

However, genotype stays the same so next generation are not saved from condition

Group Exercise

Punnet Squares and Patterns of Inheritance

KaryotypesThe arranged representation of the chromosomal make-up of a cell nucleus

Chromosomal Abnormalities

Abnormalities in number of chromosomes Caused by nondisjunction:

failure of homologous chromosomes or sister chromatids to separate properly into different progeny cells

Monosomy - condition in which one chromosome of a pair is missing from a somatic cell

Monosomy X - Turners Syndrome

Monosomy--Turner’s Syndrome

Chromosomal Abnormalities

Trisomy - condition in which one chromosome in the pair is pesent in three copies in a somatic cell

Down Syndrome (21), Trisomy 13 or 18

Klinefelter’s Syndrome - XXY

Abnormalities of Chromosome NumberTrisomy

Chromosomal Structural Abnormalities

Deletions - absence of normal chromosomal material; can be terminal or interstitial

Duplications - presence of an extra copy of a chromosomal segment

Inversions - Intrachromosomal re-arrangement such that the rearranged section is inverted

Ring Chromosome - Fusion of the ends of a chromosome that forms a circle or ring

Chromosomal Structural Abnormalities

Translocations - Interchromosomal rearrangement; can be balanced (all chromosomal material is present) or unbalanced (chromosomal material has been gained or lost); can be reciprocal or Robertsonian

Structural Abnormalities

Group Exercise

Karyotype CD-Rom

Congenital Anomalies

Structural abnormalities present at birth

Are usually not identified with a known genetic cause

Cause may be a combination of genetic and environmental factors

Children at Risk for Congenital Anomalies

Positive family history of structual anomalies

Child with one known structural anomaly

The IUGR infantThe mentally retarded

childThe unusual appearing

child

Maternal Risk Factors

DiabetesPhenylketonuria (PKU)Seizure disorderAlcohol and substance

abuseRecurrent pregnancy loss

Teratogens

Environmental substances or exposures that result in functional or structural disability.

Any agent which when given to or ingested by a pregnant woman can produce a permanent morphologic or functional abnormality.

Agents Which Cause Teratogenesis

Drugs and Chemicals; Alcohol

Infections (viruses, TORCH)Radiation exposureFat-Soluble VitaminsNicotineHeat

Fetal Susceptibility to Teratogens

Gestational age at the time of exposure

Drug dosageRoute of administration of

agentGenetic predisposition of

fetus to respond to a particular agent

Gestational Susceptibility Factors

Days 1-17 Little effect

Days 18-60 Period of organogenesis Extreme sensitivity to major

structural abnormalities Days 61-270

Considerably reduced risks Functional abnormalities can still

occur

Pedigrees

A pictorial representation or diagram of the family history.

Allows visualization of relationships of affected individuals to other family members.

May indicate a pattern of inheritance

Helps pinpoint persons who should be examined or tested.

Pedigree Format

3 generations AT LEAST!!

Note name of informant

Roman numerals for generations

Number individuals on pedigree across families

Pedigree Pointers

Seek a balance between the need for asking specific versus general questions.

Ask specific questions about each individual as you construct the pedigree (birth defects, mental retardation, specific traits relevant to the diagnosis or concern)

Ask general questions about the whole family or section of a family. Can you think of any family characteristics (traits) or medical problems in more than one family member?

Pedigree Reminders

Multiple reproductive relationships “Have you had

children/pregnancies by anyone else?”

“Did you have any pregnancies prior to this relationship?”

Don’t forget half-sibs, abortions, miscarriages, stillbirths, previous marriages.

Pedigree Pointers

Indicate possible relationships “Sometimes when there is one

family member with cleft lip and palate, there are others in the family with little indentations in their lower lip, heart problems at birth, or poor vision and joint pain. Can you think of anyone in your family with anything like that?”

Use words the clients will understand seizures = fits = fainting spells

Group Exercise

Final Group Work