The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.

There have been incredible advances made in human genetics over the past 40 years. I have set out in the next few pages to describe just some of these changes and to illustrate how they unfolded through my own experiences.

The human ACTN3 gene encodes the protein α-actinin-3, a component of the contractile apparatus in fast skeletal muscle fibers. In 1999, we identified a common polymorphism in ACTN3 (R577X) that results in absence of α-actinin-3 in more than one billion people worldwide, despite the ACTN3 gene being highly conserved during human evolution. In 2003, we demonstrated that ACTN3 genotype influences elite athletic performance, and the association between ACTN3 genotype and skeletal muscle performance has since been replicated in athletes and non-athlete cohorts. We have also studied the evolution of the R577X allele during human evolution and demonstrated that the null (X) allele has undergone strong, recent positive selection in Europeans and Asian populations. We have developed an Actn3 knockout mouse model that replicates α-actinin-3 deficiency in humans and has already provided insight into the role of α-actinin-3 in the regulation of skeletal muscle metabolism, fibre size, muscle mass and contractile properties. In particular, mouse muscle lacking α-actinin-3 uses energy more efficiently, with the fast fibers displaying metabolic and contractile properties of slow oxidative fibers. While this favors endurance activities, the trade off is that the muscle cannot generate the rapid contractions needed to excel in sprinting. We propose that the shift towards more efficient aerobic muscle metabolism associated with α-actinin-3 deficiency also underlies the adaptive benefit of the 577X allele. Our future studies will focus on the effect of ACTN3 genotype on response to exercise and ageing, and the onset and severity of muscle disease phenotype.

Inherited disorders of mitochondrial oxidative phosphorylation are the most common group of inborn errors of metabolism and cause a wide range of clinical presentations. Mitochondrial DNA encodes 13 protein subunits required for oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and mutations in most of these genes cause human disease. Nuclear genes encode most of the protein subunits and all other proteins required for mitochondrial biogenesis and mitochondrial DNA replication and expression. Mutations in 64 nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial disease and many novel mitochondrial disease genes await discovery. The genetic complexity of oxidative phosphorylation means that maternal, autosomal recessive, autosomal dominant and X-linked modes of inheritance can occur, along with de novo mutations. This complexity presents a challenge in planning efficient molecular genetic diagnosis of patients with suspected mitochondrial disease. In some situations, clinical phenotype can be strongly predictive of the underlying genotype. However, more often this is not the case and it is usually helpful, particularly with pediatric patients, to determine whether the activity of one or more of the individual oxidative phosphorylation enzymes is deficient before proceeding with mutation analysis. In this review we will summarize the genetic bases of mitochondrial disease and discuss some approaches to integrate information from clinical presentation, laboratory findings, family history, and imaging to guide molecular investigation.

Disorders of eye development such as microphthalmia and anophthalmia (small and absent eyes respectively), anterior segment dysgenesis where there may be pupillary and iris anomalies, and associated cataract and glaucoma, often lead to visual impairment or blindness. Currently treatment options are limited, as much is unknown about the molecular pathways that control normal eye development and induce the aberrant processes that lead to ocular defects. Mutation detection rates in most of the known genes are generally low, emphasizing the genetic heterogeneity of developmental ocular defects. Identification of the disease genes in these conditions improves the clinical information available for affected individuals and families, and provides new insights into the underlying biological processes for facilitation of better treatment options. Investigation of chromosomal rearrangements associated with an ocular phenotype has been especially powerful for disease gene identification. Molecular characterization of such rearrangements, which pinpoints the region by physically disrupting the causative gene or its regulatory sequences, allows for rapid elucidation of underlying genetic factors that contribute to the phenotype. Genes including PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4 have been identified in this way to be associated with developmental eye disorders. More recently, new methods in chromosomal analysis such as comparative genomic hybridization (CGH) microarray, have also enhanced our ability in disease gene identification.

As the results of the Human Genome Project are realized, it has become technically possible to identify carriers of numerous autosomal and X-linked recessive disorders. Couples at risk of having a child with one of these conditions have a number of reproductive options to avoid having a child with the condition should they wish. In Australia the haemoglobinopathies are the only group of conditions for which population screening is widely offered and which is government funded. In some Australian states there are also population screening programs for cystic fibrosis and autosomal recessive conditions more common in Ashkenazi Jewish individuals which are generally offered on a user pays basis. It is predicted that as consumer demand increases and testing becomes cheaper, that many people planning or in the early stages of pregnancy will have carrier screening for multiple genetic conditions. This will have significant implications for genetic counseling, laboratory and prenatal testing resources. In addition such screening raises a number of ethical issues including the value of lives of those born with genetic conditions for which screening is available.

The usefulness of monozygotic (MZ) twins for studying the efficacy of different face lift techniques is described. The data suggest that no particular procedure out of four under consideration is superior to any other. Next, reviews of recent twin studies of congenital anomalies, personality traits and coital orgasmic infrequency, and physical activity participation are presented. Finally, timely topics of public interest are also described. They include a rare birth consequence of artificial reproductive technology, an update on state legislation regarding parents' rights to decide the classroom placement of their young twins, and medical malpractice lawsuits involving premature twins.

Paula Bernstein and Elyse Schein are identical twins who were separated at 6 months of age. After spending the first few months of their lives together with a foster mother they were adopted by different families and finally reunited in 2004, when they were 35 years old. The book, Identical Strangers, written by both twins in alternating paragraphs, describes how they found each other after Elyse contacted their adoption agency with a request about information about her biological mother.

Womb Matesis dedicated to the ever-intriguing phenomenon of twinning. The book is intended for a general audience, in particular for those who are parents-to-be, pregnant couples and families with multiples.