Theory 4M: Genetics

Genetics

▪ The study of ways why genetic disorders occur.

▪ The study of heredity and the variation of inherited characteristics.

Genetic Counselling

A communication process by which the family is supplied with the information necessary to make informed decision about their unborn child. It provides information about how genetic conditions might affect you and your family.

Genetic Disorders

▪ Also referred as Inherited Disorders.

▪ Disorders that can be passed from one generation to next.

▪ Result from a disorder in gene or chromosome structure.

Cytogenetics

The study of chromosomes by light microscopy and the method by which chromosomal aberrations are identified.

Sex Cells

Mature reproductive cell produced by meiosis, with only half the number of chromosomes present in the body cells; 23 chromosomes (haploid)

Somatic Cells

Body cells containing 46 chromosomes (diploid). Multiplies by mitosis.

Genes

Basic units of heredity that determine both the physical and cognitive characteristics of people. Composed of segments of DNA, they are woven into strands in the nucleus of all body cells to form chromosomes.

Genome

The entire complement of genes carried by a cell.

Chromosomes

▪ They are several, small, complete, dark staining and more or less rod shaped that appear in the nucleus of the cells.

▪ Carries all hereditary material on tightly coiled strands of DNA.

▪ Threadlike structures of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.

Karyotype

A graphic representation of the chromosomes present - when fetal chromosomes are photographed and displayed, which can provide a definite answer about the presence or absence of chromosomal disorders.

Deoxyribonucleic Acid (DNA)

▪ Double stranded helix.

▪ Blueprint of life.

▪ Woven into strands to form the chromosomes.

Allele

▪ Alternate forms of the same gene from a sperm and an ovum.

▪ Two like genes for every trait; excluding sex chromosomes.

Phenotype

Refers to the outward appearance or the expression of genes.

Dominant Gene

The allele that produces an effect regardless of the state of the corresponding allele.

Recessive Gene

Non-dominant/one that produces an effect only when it is transmitted by both parents.

Homozygous

Having two like genes, example: AA, aa

A person who has two like genes for a trait - two healthy genes, for example (one from the mother and one from the father).

Heterozygous

Having two different genes, example: Aa

If the genes differ (a healthy gene from the mother and an unhealthy gene from the father, or vice versa).

Carrier

An individual who is heterozygous for the abnormal gene and clinically normal.

Trisomy

Abnormality in which there are three copies instead of the normal two, of a particular chromosomes.

Monosomy

Presence of only 1 chromosome.

Mosaicism

Presence of two or more sets of cells that differ in their genetic make-up but arise from single cell.

Aneuploidy

▪ Extra or missing chromosomes.

▪ A human cell having 45 or 47 chromosomes instead of the usual 46.

Gregor Mendel

Father of Modern Genetics

Homozygous Dominant

An individual with two homozygous genes for a dominant trait.

Homozygous Recessive

An individual with two genes for a recessive trait.

Complete Dominance

The dominant allele completely masks the recessive one.

Incomplete Dominance

Neither allele appears to mask the other completely.

Codominance

Both alleles are fully functional and express themselves individually when in the heterozygous condition.

Huntington's Disease

▪ Autosomal dominant disorder.

▪ Chronic and progressive affectation of the nervous system.

▪ Characterized by a progressive involuntary choreiform movement and dementia.

▪ Clinical feature: chorea (rapid, jerky, involuntary, purposeless movements), intellectual decline, personality changes.

Fascioscapulohumeral Muscular Dystrophy

▪ Autosomal dominant disorder.

▪ Disorder characterized by muscle weakness and wasting.

▪ This condition gets its name from the muscles that are affected most often: those of the face, around the shoulder blades, and in the upper arms.

Osteogenesis Imperfecta

▪ Autosomal dominant disorder.

▪ Also referred as brittled bone disease.

▪ Characterized by excessive fractures and bone deformity.

Marfan Syndrome

▪ Autosomal dominant disorder.

▪ Disorder of the connective tissue that affects the skeletal and cardiovascular systems.

▪ Caused by defects in the fibrillin-1 gene, which serves as a building block for elastic tissue.

▪ Characterized by tall and thin body structure, slender fingers, long arms and legs, curvature of the spine.

Waardenburg Syndrome

Autosomal dominant disorder. Group of genetic conditions that can cause hearing loss and changes in the colors of the hair, skin, and eyes.

Cystic Fibrosis

▪ Most fatal autosomal recessive disease.

▪ Affects both exocrine and endocrine glands that produce multi-system involvement.

▪ Clinical manifestation: productive cough, wheezing, pancreatic insufficiency, recurrent abdominal pain, biliary cirrhosis, vitamin deficiency, male and female infertility.

Albinism

▪ Autosomal recessive disorder.

▪ Total absence of pigment melanin.

Tay Sach's Disease

▪ Autosomal recessive disorder.

▪ Caused by the absence of an enzyme that helps break down fatty substances. These fatty substances, called gangliosides, build up to toxic levels in the child's brain and affect the function of the nerve cells.

▪ Clinical Features: Loss of motor skills, seizures, vision loss.

Adrenogenital Syndrome

▪ Autosomal recessive disorder.

▪ Enlargement of the adrenal glands resulting primarily from excessive secretion of androgenic hormones by the adrenal cortex.

▪ Masculinization in women, feminization in men or premature sexual development in children.

Phenylketonuria

▪ Autosomal recessive disorder.

▪ Inherited disorder that increases the levels of a substance called phenylalanine in the blood.

▪ Results in CNS damage from toxic levels of phenylalanine.

▪ Clinical Features: Musty breath and urine odor, seizure, skin rashes, blue eyes, microcephaly.

Galactosemia

▪ Autosomal recessive disorder.

▪ Disorder that affects how the body processes a simple sugar called galactose.

▪ If a diagnosed infant is given milk, unmetabolized milk sugars build up and damage the liver, eyes, kidneys and brain.

Limb-Girdle Muscular Dystrophy

▪ Autosomal recessive disorder.

▪ A group of diseases that cause weakness and wasting of the muscles in the arms and legs.

▪ The muscles most affected are those closest to the body, specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.

Rh Factor Incompatibility

▪ Autosomal recessive disorder.

▪ A condition that occurs during pregnancy if a woman has Rh-negative blood and her baby has Rh-positive blood.

X-Linked Hypophosphatemia

▪ X-linked dominant disorder.

▪ Disorder characterized by low levels of phosphate in the blood.

▪ Clinical Features: Bowed or bent legs, short stature, bone pain, and severe dental pain.

Rett Syndrome

▪ X-linked dominant disorder.

▪ A neurological and developmental disorder that affects the way the brain develops, causing a progressive loss of motor skills and speech.

▪ Clinical Features: Loss of speech, purposeful use of hands and muscle tone, gait disturbance, breathing issues, slowed growth of head, feet and hands.

Alport Syndrome

▪ X-linked dominant disorder.

▪ A genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.

Hemophilia A & B

▪ X-linked recessive disorder.

▪ A = Classic Hemophilia or Factor VIII Deficiency

▪ B = Christmas Disease or Factor IX Deficiency

▪ A bleeding disorder resulting from congenital deficiency dysfunction.

▪ Absence of specific coagulation protein factors.

Color Blindness

▪ X-linked recessive disorder.

▪ Also known as Color Deficiency.

▪ Inability to distinguish the difference between certain color.

Fragile X Syndrome

▪ X-linked recessive disorder.

▪ A genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment.

▪ Clinical Features: Broad forehead, elongated face, large prominent ears, strabismus, highly arche palette, hypotonia.

Duchenne Muscular Dystrophy

▪ X-linked recessive disorder.

▪ A disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact.

Polyploidy

▪ Multiples of the haploid chromosome number.

▪ Condition in which a normally diploid cell or organism acquires one or more additional sets of chromosomes.

Trisomy 21

▪ Also known as Down Syndrome or 47XX21 / 47XY21.

▪ Frequently occurring chromosomal disorder.

▪ Clinical Features: Nose is broad and flat, brushfield spots (white specks on iris), protruding tongue, short neck, low-set ears, poor muscle tone, short and thick fingers, peculiar crease on palms.

Trisomy 18

▪ Also known as Edwards' Syndrome or 47XX18 / 47XY18

▪ Clinical Features: Severely cognitively challenged, SGA, low-set ears, small jaw, congenital heart defects, misshapen fingers, rocker-bottom feet.

▪ Can't survive beyond infancy.

Trisomy 13

▪ Also known as Patau Syndrome or 47XX13 / 47XY13

▪ Clinical Features: Severely cognitively challenged, cleft and lip palate, abnormal genitalia, microcephaly, microphthalmos, low-set ears.

▪ Can't survive beyond early childhood.

Turner Syndrome

▪ Also known as Gonadal Dysgenesis or 45X0.

▪ Clinical Feature: Short in stature, streak ovaries, sterile, absence of pubic hair, webbed and short neck, sterile.

Klinefelter Syndrome

▪ 47XXY

▪ Males with extra X chromosomes.

▪ Clinical Features: Gynecomastia, failure of secondary sex characteristics to develop at puberty, small testes, infertile.

47, XXX Females

Tall for their families, slight reduction in IQ, normal fertility.

47, XXY Males

Taller than average but have normal phenotype, ADHD.

Translocations

Situations in which a child gains an additional chromosomes through yet another route.

Balanced Translocations

One parent of a child has 46 chromosomes but chromosome 21 is misplaced, instead of standing alone, it is abnormally attached to another chromosomes, such as 14. The parent's appearance and functioning are normal because the total chromosome count is a normal 46.

Unbalanced Translocations

During meiosis, the abnormal chromosome 14 (carrying the extra 21 chromosome) and the normal chromosome from the other parent are both included in one sperm or ovum, the resulting child will have a total of 47 chromosomes because of the extra number 21.

Inversions

▪ Results from two breaks on a chromosome with inversion of a segment and reinsertion at its original site.

▪ Non-viable to conception.

Deletions

▪ A part of a chromosome breaks during cell division.

▪ Causes the affected person to have the number of chromosomes plus or minus an extra portion of chromosomes, such as 45.75 or 47.25.

Cri-Du-Chat Syndrome

A partial deletion on the short arm (p) of chromosome 5.

Classical Karyotyping

▪ Sample of peripheral venous blood or a scraping of cells from the buccal membrane is taken.

▪ Lymphocytes are identified and allowed to grow until they reach metaphase or prophase.

▪ Cells are then stained, placed under a microscope and photographed.

Molecular Karyotyping

▪ Using chromosome microarray analysis (CMA)

▪ Studies individual genes rather than chromosomes.

▪ Detects even more than classical karyotyping.

▪ First tier for prenatal diagnosis.

▪ Diseases that can be identified: cystic fibrosis, huntington's disease, fragile x syndrome, hemophilia, and Duchenne muscular dystrophy.

Maternal Serum Screening

▪ Sample of maternal blood can be examined for a karyotyping and fetal DNA.

▪ Advantage: Noninvasive and no risk of fetal infection.

Nuchal Translucency Screening

▪ Sonogram taken during the first trimester.

▪ Measures the thickness of the fluid buildup at the back of the developing baby's neck.

▪ Diseases Identified: Down Syndrome, Turner Syndrome.

Chorionic Villi Sampling

▪ Highly accurate but possess great risks.

▪ Chorion cells are located by ultrasound as a thin catheter is inserted vaginally and a number of chorionic cells are removed for analysis; cells removed will then be submitted for karyotyping and or DNA analysis.

Amniocentesis

▪ Withdrawal of amniotic fluid through the abdominal wall at 15th to 20th week gestation.

▪ A needle is inserted transabdominally guided with ultrasound, 20 mL of amniotic fluid is aspirated.

Percutaneous Umbilical Blood Sampling (PUBS)

▪ Also known as Cordocentesis.

▪ Removal of blood from the fetal umbilicus cord at 17 weeks using an amniocentesis technique.

Fetal Imaging

▪ Also used to assess a fetus for general size and structural disorders of the internal organs, spine, limbs.

▪ Ex. MRI and Ultrasound

Fetoscopy

▪ Insertion of a fiber optic fetoscope through a small incision in the mother's abdomen into the uterus and membranes.

▪ Done under local anesthesia.

Newborn Screening

Blood heel prick analysis 24 to 48 hours after birth.

Preimplantation Diagnosis

▪ Applicable to IVF procedures.

▪ Both sperm and ova are assessed before implantation.

Artificial Insemination by Donor (AID)

▪ For couples with a male who can't produce an offspring.

▪ Sperm of an anonymous or safe sperm donor or through a sperm bank is used to impregnate a woman.

▪ The sperm is injected into the uterus of the cervical canal through a special cannula.

Surrogate Mother

A woman who agrees to be alternately inseminated, typically by the male partner's sperm and bear a child for the couple.